Title

A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

🤖 Abstract

## Understanding the Role of Nucleocapsid Protein in SARS-CoV-2 Viral RNA Genome Processing The nucleocapsid protein plays a crucial role in viral RNA genome processing, allowing it to interact with the virus's RNA genome. ## Insights from High-Resolution Structures and Mutations Hybrid structures have been obtained for the N-terminal domain (NTD) of the nucleocapsid protein, providing valuable information on how it interacts with viral RNA. However, determining the exact mechanism of complex formation remains elusive. Research has also investigated how mutations in the nucleocapsid NTD affect its stability and ability to interact with RNA. Crystallography and solution nuclear magnetic resonance (NMR) studies have been used to analyze this process. ## Key Findings The core network of residues within the nucleocapsid protein, particularly those found in Betacoronaviruses, is crucial for maintaining protein stability and facilitating communication between flexible loop regions that allow for RNA recognition. This network guides specific interactions with viral RNA. ## Proposed Explanation Based on its structural analysis, the NTD is proposed to be evolutionarily robust, allowing it to maintain its functions in RNA processing despite mutations. The core network within this domain serves as a key factor in these processes. The final answer is: The nucleocapsid protein plays a crucial role in viral RNA genome processing by interacting with the virus's RNA genome. A comprehensive analysis of high-resolution structures and mutation effects has provided insights into how it functions, including its structure, stability, and interactions with RNA.

Abstract

The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive. Similarly, the molecular impact of nucleocapsid NTD mutations that have emerged since 2019 has not yet been fully explored. Using crystallography and solution NMR, we investigate how NTD mutations influence structural integrity and RNA-binding. We find that both features rely on a core network of residues conserved inBetacoronaviruses, crucial for protein stability and communication among flexible loop-regions that facilitate RNA-recognition. Our comprehensive structural analysis demonstrates that contacts within this network guide selective RNA-interactions. We propose that the core network renders the NTD evolutionarily robust in stability and plasticity for its versatile RNA processing roles.

Article URL: https://www.nature.com/articles/s41467-024-55024-0

Title

The comprehensive SARS-CoV-2 ‘hijackome’ knowledge base

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: A new study looks at how different types of COVID-19 variants affect the cells that host viruses. The researchers wanted to know more about how these variants change and which proteins are involved in the process. They studied changes in thousands of proteins over time, and found some differences between each variant. This helps us better understand how viral proteins work and why some variants might be harder for treatment to target.

Abstract

The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.1 and BA.5 variants over time frames extending from 1 to 36 h post infection. Our results revealed distinct temporal patterns of protein expression across the VOCs, with notable differences in the (phospho)proteome dynamics that suggest variant-specific adaptations. Specifically, we observed enhanced expression and activation of key components within crucial cellular pathways such as the RHO GTPase cycle, RNA splicing, and endoplasmic reticulum-associated degradation (ERAD)-related processes. We further utilized proximity biotinylation mass spectrometry (BioID-MS) to investigate how specific mutation of these VOCs influence viral–host protein interactions. Our comprehensive interactomics dataset uncovers distinct interaction profiles for each variant, illustrating how specific mutations can change viral protein functionality. Overall, our extensive analysis provides a detailed proteomic profile of host cells for each variant, offering valuable insights into how specific mutations may influence viral protein functionality and impact therapeutic target identification. These insights are crucial for the potential use and design of new antiviral substances, aiming to enhance the efficacy of treatments against evolving SARS-CoV-2 variants.

Article URL: https://www.nature.com/articles/s41421-024-00748-y

Title

Exploring social determinants of health and their impacts on self-reported quality of life in long COVID-19 patients

🤖 Abstract

This study investigates how people with long COVID experience their quality of life. It looked at 3,463 patients in British Columbia's post-COVID-19 recovery clinics to find out how well they're functioning. The results show that many people had significant problems with daily activities and were unhappy. The factors that affected people's well-being were not the same for everyone. Some aged 50 or older had fewer problems than younger people. Men, women, and ethnic minorities also had different impacts on their quality of life. For example, older age made some people less anxious and depressed but more pain-free. However, this study found that many people with long COVID were not just dealing with physical symptoms - they also felt sad or hopeless. The researchers conclude that addressing the social determinants of health can help people with long COVID improve their quality of life. They suggest using targeted strategies to make recovery easier for different groups. This could lead to better overall health outcomes and support policymakers develop more effective public health measures.

Abstract

This study explores the health-related quality of life (HRQoL) experienced by patients with Long COVD-19 using data from British Columbia’s post-COVID-19 Recovery Clinics. A retrospective cohort of 3463 patients was analyzed to assess HRQoL through the EQ-5D-5L questionnaire which includes five dimensions (mobility, self-care, usual activities, physical health, and mental health) administered to patients; responses were analyzed using the Visual Analogue Score (VAS). Notably, 95% of participants reported HRQoL scores below 90, with 50% scoring under 60, indicating significant impacts on their well-being. The analysis revealed that HRQoL is significantly influenced by various social determinants of health (SDoH), including age, sex, employment status, and ethnicity, each showing distinct correlations with HRQoL dimensions and overall VAS scores. Specifically, older age was associated with decreased mobility and increased pain/discomfort but less anxiety and depression, highlighting varying impacts across the age spectrum. The study highlights the multifaceted impacts of Long COVID on the lives of patients and underscores the necessity of targeted strategies to improve HRQoL among diverse groups, considering specific SDoH. Such a comprehensive approach could lead to more equitable health outcomes and support the development of tailored public health policies aimed at the recovery and rehabilitation of Long COVID sufferers.

Article URL: https://www.nature.com/articles/s41598-024-81275-4

Title

Respiratory syncytial virus glycoprotein G impedes CX3CR1-activation by CX3CL1 and monocyte function

🤖 Abstract

The Respiratory Syncytial Virus (RSV) has a protein called soluble form (sG) that is similar in structure and function to a chemokine called fractalkine (CX3CL1). This similarity suggests that sG might interact with CX3CR1, a receptor on immune cells. We studied two versions of RSV sG: one normal version (WT) and another version that has lost the part of the protein responsible for binding to CX3CL1. We found that these versions of RSV sG do not directly activate CX3CR1 but instead compete with CX3CL1 for its receptor binding. This competition can limit how well the immune system responds to X (a chemokine) when it binds to Y (CX3CR1). In our research, we discovered that the protein RSV sG might help reduce the host's immune response if they were in contact with this virus.

Abstract

The soluble form of the Respiratory Syncytial Virus (RSV) G protein (sG) bears resemblance to the chemokine fractalkine (CX₃CL1). Both RSV sG and CX3CL1 possess a mucin-like domain and a CX3C motif, exist in membrane-associated and soluble forms, and bind to the CX₃CR1 receptor expressed on immune and epithelial cells. To explore the biological significance of RSV sG and CX₃CR1 interaction, we produced wild type (WT) and CX₃C motif-deficient (CX3CMut) RSV sG proteins and determined their effects on CX₃CR1 signaling in monocytic cells. Both CX3CMut- and WT RSV sG failed to activate CX₃CR1 signaling directly. However, WT sG competed with CX₃CL1 for CX₃CR1 binding and reduced CX3CL1-induced CX₃CR1-activation, monocyte migration, and adhesion. The CX₃C motif of sG was crucial for competitive blocking of CX3CL1-mediated activation, as CX₃CMutsG did not affect these CX₃CR1 functions significantly. Thus, blockade of CX₃CR1 signaling by sG may allow RSV to dampen host immune responses.

Article URL: https://www.nature.com/articles/s44298-024-00075-9

Title

Repurposing raltegravir for reducing inflammation and treating cancer: a bioinformatics analysis

🤖 Abstract

### Abstract ### The body has a way to defend itself against harm, called inflammation. A protein called ADAM17 plays a key role in this process. In some cases, it can also cause more inflammation or harm. To study this, scientists looked at how five drugs work and identified which ones might help stop ADAM17 from causing too much of an inflammatory response. They chose to test these drugs because they are already FDA-approved and have been shown to be effective in treating other conditions. Using computer programs to analyze the data, scientists found that one drug called Raltegravir is particularly good at stopping inflammation caused by faulty ADAM17 and has a good safety profile.

Abstract

Inflammation is a defensive mechanism that safeguards the human body against detrimental stimuli. Within this intricate process, ADAM17, a zinc-dependent metalloprotease, emerges as an indispensable element, fostering the activation of diverse inflammatory and growth factors within the organism. Nonetheless, ADAM17 malfunctions can augment the rate of growth, inflammatory factors, and subsequent damage. Thus, in this study, we examined and repurposed drugs to suppress the activity of ADAM17. To this end, we employed bioinformatics techniques such as molecular docking, molecular dynamics, and pharmacokinetic studies. Five FDA-approved drugs including Raltegravir, Conivaptan, Paclitaxel, Saquinavir, and Venetoclax with the ability to impede the activity of the ADAM17 metalloenzyme were identified. Moreover, these drugs did not include strong zinc-binding functional groups when verified by the ACE functional group finder. However, furtherin silicoanalysis has indicated that Raltegravir demonstrates a commendable interaction with the active site amino acids and exhibits the most favorable pharmacokinetic properties compared to others. Considering the results of bioinformatics tools, it can be concluded that Raltegravir as an antiviral drug could be repurposed to prevent severe inflammatory response and tumorigenesis resulting from ADAM17 malfunction.

Article URL: https://www.nature.com/articles/s41598-024-82065-8

Title

A quantitative, label-free visual interference colour assay platform for protein targeting and binding assays

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Imagine being able to visualize how different molecules interact with each other without using special equipment or expensive machines. Researchers have developed an innovative way to do this called "Visual Interference Color Assay" (VICA). It uses a special surface that changes color when molecules from different types of proteins come together, allowing scientists to see exactly what's happening in real-time. This technology is useful for studying complex protein interactions and can also be used to analyze blood or other bodily fluids.

Abstract

The vast array of immunoassay technologies used to assess protein interactions is costly or platform-specific. We present a label-free visual interference colour assay (VICA) that quantifies peptide and protein interactions by creating an iridescent surface allowing direct visualisation without spectrophotometric optics or microfluidics. A nanoporous aluminium oxide surface is tuned to match the refractive indices of the overlying protein layers to generate visual interference colours. To functionalise the surface, we created an affinity-capture system using a protein A-carboxyglutamic (GLA) construct that orients antibodies to enhance the signal. Using off-the-shelf antibodies, the platform can isolate analytes in buffer, whole blood, or serum. This surface generates a discernible colour change at concentrations as low as 50 femtomoles/mm2and can monitor oligomer formation in sequential steps on the same slide. VICA provides comparable kinetic parameters to biolayer interferometry and traditional immunoassays while also allowing characterisation of proteins in large macromolecular complexes.

Article URL: https://www.nature.com/articles/s44328-024-00017-8

Title

Predictors of dropout in cognitive behavior and interpersonal online brief psychotherapies for essential professionals during the COVID-19 pandemic

🤖 Abstract

Understanding predictors of premature dropout from psychotherapy can help identify who is most at risk of dropping out and provide targeted interventions to reduce this risk. A study analyzing data from online therapy sessions for COVID-19 pandemic survivors found that certain factors, such as having children or living in specific regions, were associated with a higher likelihood of dropping out. The study also identified the need for culturally tailored strategies, support for families with young children, and therapy focused on low life satisfaction.

Abstract

Premature dropout from psychotherapy can harm patients and increase mental health costs. This study identified predictors of dropout in brief online psychotherapy for essential workers during the COVID-19 pandemic. This was a secondary analysis of a randomized trial on 4-week CBT or IPT protocols. Participants provided sociodemographic data and completed the Patient-Reported Outcomes Measurement Information System and Burnout Assessment Tool Short-Form. Predictors were analyzed in three blocks: sociodemographic, clinical, and therapist characteristics using bivariable and multivariable analyses. The sample included 804 individuals who attended at least the first session of either CBT (n= 403) or IPT (n= 401). A total of 17.2% (n= 138) of the participants dropped out during the protocol. Significant predictors of dropout included having children (IRR = 1.48; 95% CI: 1.07–2.05;p= 0.016), residing in specific regions of Brazil (Northeast IRR = 1.44; 95% CI:1.04–2.00;p= 0.02 and Midwest IRR = 1.73; 95%CI: 1.13–2.64;p= 0.01), therapist male sex (IRR = 2.04; 95% CI: 1.47–2.83; p = < 0.001), second wave of Covid-19 (IRR = 1.54; 95% CI: 1.01–2.34;p= 0.04) and low life satisfaction (IRR = 1.63; 95% CI: 1.06–2.50;p= 0.02). Our findings underscore the necessity for culturally tailored strategies, support for those with children, and targeted therapy for individuals with low life satisfaction. Implementation of these strategies may reduce dropout rates and improve treatment outcomes for essential workers in crisis.

Article URL: https://www.nature.com/articles/s41598-024-81327-9

Title

SARS-CoV-2 N protein recruits G3BP to double membrane vesicles to promote translation of viral mRNAs

🤖 Abstract

Ras-GTPase-activating protein SH3-domain-binding proteins (G3BP) play a critical role in forming stress granules (SGs), which are important for virus replication and pathogenesis. The SARS-CoV-2 nucleocapsid (N) protein has a strong affinity for G3BP, causing it to inhibit the formation of SGs after infection. To study this interaction, researchers created a mutant version of the N protein that lacks the binding site for G3BP. This mutation leads to an increased and prolonged response in infected cells, which results in reduced replication and pathogenesis.

Abstract

Ras-GTPase-activating protein SH3-domain-binding proteins (G3BP) are critical for the formation of stress granules (SGs) through their RNA- and ribosome-binding properties. SARS-CoV-2 nucleocapsid (N) protein exhibits strong binding affinity for G3BP and inhibits infection-induced SG formation soon after infection. To study the impact of the G3BP-N interaction on viral replication and pathogenesis in detail, we generated a mutant SARS-CoV-2 (RATA) that specifically lacks the G3BP-binding motif in the N protein. RATA triggers a stronger and more persistent SG response in infected cells, showing reduced replication across various cell lines, and greatly reduced pathogenesis in K18-hACE2 transgenic mice. At early times of infection, G3BP and WT N protein strongly colocalise with dsRNA and with non-structural protein 3 (nsp3), a component of the pore complex in double membrane vesicles (DMVs) from which nascent viral RNA emerges. Furthermore, G3BP-N complexes promote highly localized translation of viral mRNAs in the immediate vicinity of the DMVs and thus contribute to efficient viral gene expression and replication. In contrast, G3BP is absent from the DMVs in cells infected with RATA and translation of viral mRNAs is less efficient. This work provides a fuller understanding of the multifunctional roles of G3BP in SARS-CoV-2 infection.

Article URL: https://www.nature.com/articles/s41467-024-54996-3

Title

A landscape of X-inactivation during human T cell development

🤖 Abstract

Females have an enhanced immune response to both self-antigens and non-self-antigens, but this comes at the cost of being more prone to autoimmune diseases. Research on how females respond differently to different types of threats may hold clues about why they're more likely to develop certain conditions. A study found that X-linked genes in female T cells are responsible for their strong immune response. By analyzing data from thymocytes (immature white blood cells) from healthy males, females, a woman with skewed X-chromosome inactivation, and individuals with Turner syndrome, scientists created detailed maps of how T cells develop and get out of control when they should stay inactivated. The results show that the X chromosome is stable throughout T cell development and independent of genes involved in its initial activation. Furthermore, certain genes typically escaping XCI are expressed only from one X-chromosome, while a second X-chromosome seems unnecessary for T cell development. This new understanding of XCI may lead to re-evaluating sex differences in immune function.

Abstract

Females exhibit a more robust immune response to both self-antigens and non-self-antigens than males, resulting in a higher prevalence of autoimmune diseases but more effective responses against infection. Increased expression of X-linked immune genes in female T cells is thought to underlie this enhanced response. Here we isolate thymocytes from pediatric thymi of healthy males (46, XY), females (46, XX), a female with completely skewed X-chromosome inactivation (46, XX, cXCI) and a female with Turner syndrome (45, X0). Using whole exome sequencing, RNA sequencing and DNA methylation data, we present a sex-aware expression profile of T cell development and generate a high-resolution map of escape from X-chromosome inactivation (XCI). Unexpectedly, XCI is transcriptionally and epigenetically stable throughout T cell development, and is independent of expression ofXIST, the lncRNA responsible for XCI initiation during early embryonic development. In thymocytes, several genes known to escape XCI are expressed from only one X-chromosome. Additionally, we further reveal that a second X-chromosome is dispensable for T cell development. Our study thus provides a high-resolution map of XCI during human development and suggests a re-evaluation of XCI in sex differences in T cell function.

Article URL: https://www.nature.com/articles/s41467-024-54110-7

Title

A 24-month National Cohort Study examining long-term effects of COVID-19 in children and young people

🤖 Abstract

Background: Many children and young people (CYP) infected with SARS-CoV-2 experience impairing symptoms post-infection. Methods: We studied 31,012 CYP in England aged 11-17 who had a PCR test between September 2020 and March 2021. Of those who tested positive, we followed them up to 24 months later. Results: Only 7.2% of the group fulfilled the criteria for post-COVID-19 condition (PCC). This was found in different groups based on whether they had initial tests come back negative or positive, and if they were reinfected. Conclusions: The study highlights that PCC is more common in older CYPs and those from disadvantaged areas. It also shows that symptom severity/impact increases for CYP who fulfill the criteria for PCC.

Abstract

BackgroundSome children and young people (CYP) infected with SARS-COV-2 experience impairing symptoms post-infection, known as post-COVID-19 condition (PCC). Using data from the National Long COVID in Children and Young People (CloCk) study, we report symptoms and their impact up to 24-months post-infection.MethodsCloCk is a cohort of CYP in England aged 11-to-17-years when they had a SARS-CoV-2 PCR-test (between September 2020 and March 2021). Of 31,012 eligible CYP 24-months post-PCR test, 12,632 participated (response = 40.7%). CYP were grouped by infection status: ‘initial test-negatives; no subsequent positive-test’ (NN); ‘initial test-negatives; subsequent positive-test’ (NP); ‘initial test-positives; no reported re-infection’ (PN); and ‘initial test-positives; reported re-infection’ (PP). The Delphi research definition of PCC in CYP was operationalised; symptom severity/impact and validated scales (e.g., Chalder Fatigue Scale) were recorded. We examine symptom profiles 24-month post-index-test by infection status.Results7.2% of CYP consistently fulfil the PCC definition at 3-, 6-, 12- and 24-months. These CYPs have a median of 5-to-6 symptoms at each time-point. Between 20% and 25% of all infection status groups report 3+ symptoms 24-months post-testing; 10–25% experience 5+ symptoms. The reinfected group has more symptoms than the other positive groups; the NN group has the lowest symptom burden (p< 0.001). PCC is more common in older CYPs and in the most deprived. Symptom severity/impact is higher in those fulfilling the PCC definition.ConclusionsThe discrepancy in the proportion of CYP fulfilling the Delphi PCC definition at 24-months and those consistently fulfilling the definition across time, highlights the importance of longitudinal studies and the need to consider clinical impairment and range of symptoms.

Article URL: https://www.nature.com/articles/s43856-024-00657-x

Title

Edge-centric connectome-genetic markers of bridging factor to comorbidity between depression and anxiety

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: A type of mental health condition called depression often goes hand-in-hand with anxiety. However, many people who experience both symptoms struggle to find meaning and pattern in their experiences, making it hard for doctors and therapists to diagnose and treat them. Researchers developed a way to identify specific characteristics or "factors" that are common to both depression and anxiety, which they called the common bridging factor (cbfactor). They found 12 key features of these factors in people with both conditions. This cbfactor can also be used to predict what might cause similar symptoms in others. The researchers looked at brain connections in twins who were diagnosed with both conditions, and found that the patterns of brain activity were influenced by genetics. They also identified specific genes and brain regions that are involved in regulating emotional responses and developing brains. This study has helped us better understand how depression and anxiety share underlying characteristics and how they might be linked to similar problems in other areas of life.

Abstract

Depression-anxiety comorbidity is commonly attributed to the occurrence of specific symptoms bridging the two disorders. However, the significant heterogeneity of most bridging symptoms presents challenges for psychopathological interpretation and clinical applicability. Here, we conceptually established a common bridging factor (cbfactor) to characterize a general structure of these bridging symptoms, analogous to the general psychopathologicalpfactor. We identified acbfactor from 12 bridging symptoms in depression-anxiety comorbidity network. Moreover, thiscbfactor could be predicted using edge-centric connectomes with robust generalizability, and was characterized by connectome patterns in attention and frontoparietal networks. In an independent twin cohort, we found that these patterns were moderately heritable, and identified their genetic connectome-transcriptional markers that were associated with the neurobiological enrichment of vasculature and cerebellar development, particularly during late-childhood-to-young-adulthood periods. Our findings revealed a general factor of bridging symptoms and its neurobiological architectures, which enriched neurogenetic understanding of depression-anxiety comorbidity.

Article URL: https://www.nature.com/articles/s41467-024-55008-0

Title

A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins

🤖 Abstract

Metastasis drives significant scientific interest in studying the interactions between the immune system and cancer progression. We developed a multiscale mathematical model to simulate how the immune system responds to cancer growth in general epithelial tissue. Our results show that the model can generate diverse patient trajectories, including uncontrolled growth, partial response, and complete immune response. Our analysis revealed key factors that influence simulated immunosurveillance, helping us identify parameter settings with significant impact. This study contributes to the field of cancer patient digital twins (CPDTs), enabling clinicians to better understand individual patient complexities in cancer treatment decisions. However, we acknowledge several challenges remain before CPDTs can be fully realized, including uncertainties in immune responses, unreliable patient stratification, and unpredictable personalized treatments.

Abstract

Metastasis is the leading cause of death in patients with cancer, driving considerable scientific and clinical interest in immunosurveillance of micrometastases. We investigated this process by creating a multiscale mathematical model to study the interactions between the immune system and the progression of micrometastases in general epithelial tissue. We analyzed the parameter space of the model using high-throughput computing resources to generate over 100,000 virtual patient trajectories. We demonstrated that the model could recapitulate a wide variety of virtual patient trajectories, including uncontrolled growth, partial response, and complete immune response to tumor growth. We classified the virtual patients and identified key patient parameters with the greatest effect on the simulated immunosurveillance. We highlight the lessons derived from this analysis and their impact on the nascent field of cancer patient digital twins (CPDTs). While CPDTs could enable clinicians to systematically dissect the complexity of cancer in each individual patient and inform treatment choices, our work shows that key challenges remain before we can reach this vision. In particular, we show that there remain considerable uncertainties in immune responses, unreliable patient stratification, and unpredictable personalized treatment. Nonetheless, we also show that in spite of these challenges, patient-specific models suggest strategies to increase control of clinically undetectable micrometastases even without complete parameter certainty.

Article URL: https://www.nature.com/articles/s41540-024-00472-z

Title

SARS-CoV-2 Nsp6-Omicron causes less damage to theDrosophilaheart and mouse cardiomyocytes than ancestral Nsp6

🤖 Abstract

Here's a simplified version of the abstract: Scientists studied the genetic material of SARS-CoV-2 to understand why it causes fewer severe illnesses compared to other versions. They found that an old, but still very contagious, strain has changed in certain parts, making it less likely to harm people. By comparing this strain with another version, they discovered which part is responsible for its reduced pathogenicity and how it affects different tissues. This research suggests that the amino acid changes in this particular SARS-CoV-2 strain may have made it less capable of causing disease.

Abstract

A few years into the COVID-19 pandemic, the SARS-CoV-2 Omicron strain rapidly becomes and has remained the predominant strain. To date, Omicron and its subvariants, while more transmittable, appear to cause less severe disease than prior strains. To study the cause of this reduced pathogenicity we compare SARS-CoV-2 ancestral Nsp6 with Nsp6-Omicron, which we have previously identified as one of the most pathogenic viral proteins. Here, through ubiquitous expression inDrosophila, we show that ancestral Nsp6 causes both structural and functional damage to cardiac, muscular, and tracheal (lung) tissue, whereas Nsp6-Omicron has minimal effects. Moreover, we show that ancestral Nsp6 dysregulates the glycolysis pathway and disrupts mitochondrial function, whereas Nsp6-Omicron does not. Through validation in mouse primary cardiomyocytes, we find that Nsp6-induced dysregulated glycolysis underlies the cardiac dysfunction. Together, the results indicate that the amino acid changes in Omicron might hinder its interaction with host proteins thereby minimizing its pathogenicity.

Article URL: https://www.nature.com/articles/s42003-024-07307-x

Title

TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: A new virus called SARS-CoV-2 causes COVID-19. The virus makes cells in our body very sick and can also cause damage to tissues. Research has found that a specific protein on the surface of the virus, called M, is being blocked by a protein called TRIM7 from killing cells. When this happens, more viral particles are released into the body. Scientists have studied this process and found that mutations in the M-K14 region of the virus made it less infectious. They also found that these mutations affected how the virus interacts with the cell's immune system. The study suggests that TRIM7 may be a new target for developing antiviral treatments to fight against SARS-CoV-2.

Abstract

SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. Here we show that the host E3-ubiquitin ligase TRIM7 acts as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein.Trim7-/-mice exhibit increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients reveal that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus shows reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

Article URL: https://www.nature.com/articles/s41467-024-54762-5

Title

Risk of canine distemper virus vaccination of domestic dogs in giant panda habitat to giant pandas

🤖 Abstract

Here's a simplified version of the abstract: A giant panda is vulnerable to a virus called canine distemper that can be spread by infected dogs. Scientists studied 69 vaccinated dogs in their habitats to see if they could safely share food or space with wild pandas without getting sick. The results showed that the vaccinated dogs were more likely to shed the virus, and those who had higher levels of antibodies against the virus were less likely to do so. To protect both humans and wildlife, experts recommend limiting access to vaccinated dogs for at least three weeks after vaccination and encouraging cooperation from local authorities and reserve managers to manage domestic dog populations effectively.

Abstract

The giant panda(Ailuropioda melanoleuca), a unique relic species in China and a global biodiversity conservation symbol, faces the threat of canine distemper virus (CDV). Vaccinating domestic dogs in panda habitats against CDV is crucial, yet the associated risks remain understudied. We investigated the safety of CDV vaccination in 69 domestic dogs within panda habitats, employing enzyme-linked immunosorbent assay for CDV antibodies and quantitative reverse transcription polymerase chain reaction for viral RNA, a marker of viral shedding. Results revealed that vaccinated dogs posed a risk through viral shedding, mainly starting from the ninth day post-vaccination. Unvaccinated dogs exhibited increased CDV antibodies and subsequent shedding, with phylogenetic analysis confirming infection from vaccinated dogs in shared kennels. Dogs with higher initial antibodies displayed reduced shedding and a markedly abbreviated shedding duration (6.7 days) than those with lower initial antibodies (9.8 days). Habitat area analysis revealed substantial overlaps between domestic dogs and wild giant pandas in two nature reserves in China. To safeguard wildlife, particularly giant pandas, we recommend restricting vaccinated dogs’ activity for at least three weeks post-vaccination, complementing existing management practices. We advocate collaborative efforts among local authorities, reserve management and villagers for effective vaccination and post-vaccination management of domestic dogs.

Article URL: https://www.nature.com/articles/s41598-024-79806-0

Title

Lightweight convolutional neural network for chest X-ray images classification

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: We created a special kind of computer program called a neural network for image analysis on chest X-rays. Our goal was to make this program as fast and efficient as possible, so it could analyze images quickly and accurately. We used data from real COVID-19 cases in the past year to test our program. The results showed that we were able to correctly identify three main categories of people: those with COVID-19, pneumonia, or no symptoms at all. This means the program can help doctors make quicker decisions about who needs medical attention for COVID-19.

Abstract

In this study, we developed a lightweight and rapid convolutional neural network (CNN) architecture for chest X-ray images; it primarily consists of a redesigned feature extraction (FE) module and multiscale feature (MF) module and validated using publicly available COVID-19 datasets. Experiments were conducted on multiple updated versions of the COVID-19 Radiography Database, a publicly accessible dataset on Kaggle. The database contained images categorized into three classes: COVID-19 coronavirus, viral or bacterial pneumonia, and normal. The results revealed that the proposed method achieved a training accuracy of 99.85% and a validation accuracy of 96.28% when detecting the three classes. In the test set, the optimal results were 96.03% accuracy for COVID-19, 97.10% accuracy for viral or bacterial pneumonia, and 97.86% accuracy for normal individuals. By reducing the computational requirements and improving the speed of the model, the proposed method can achieve real-time, low-error performance to help medical professionals with rapid diagnosis of COVID-19.

Article URL: https://www.nature.com/articles/s41598-024-80826-z

Title

Features of chronic urticaria after COVID-19 mRNA vaccine over time

🤖 Abstract

Background: New onsets of chronic urticaria (CU) have been linked to repeated immunizations, particularly with Moderna mRNA-1273. Methods: Researchers monitored 50 people with CU after COVID-19 mRNA vaccination through two surveys and compared their features with 135 without a history of urticaria. They tested for anti-vaccine IgE, SARS-Cov2 humoral response, and atopy surrogate markers. Results: Post-vaccination CU often appears within 10 days and is more common in middle-aged individuals (66%). In 2023, cases remained active in 53% of the remaining patients. Dermographism was present in 54% (2022) and 61% (2023). Bat positivity is associated with higher neutralizing activities against SARS-Cov2, but not directly linked to CU or atopy. Conclusions: The mRNA-1273 vaccine booster induces anti-vaccine IgE independently of CU. This suggests that the vaccine may trigger CU in some individuals, potentially through a previously unknown mechanism.

Abstract

BackgroundNew onsets of chronic urticaria (CU) have been reported after repeated immunizations, mainly with the Moderna mRNA-1273 vaccine (Spikevax). This study aims to evaluate patients with CU after COVID-19 mRNA vaccination. The contribution of SARS-Cov2 infection, atopy and IgE against the vaccine was analyzed.MethodsWe monitored the features of patients who developed CU after vaccination through two surveys conducted in 2022 and 2023. Fifty individuals with CU underwent blood tests, and their results were compared with individuals without a history of urticaria (N= 135). The presence of anti-vaccine IgE was tested in 185 individuals with basophil activation tests (BAT). We assessed anti-SARS-Cov2 humoral response, and the presence of IgEs against common respiratory allergens (Phadiatop) as a surrogate for atopy.ResultsPost-vaccination CU occurs after a median interval of 10 days and significantly more after the Spikevax booster, affecting middle-aged individuals (median 41, 66% females). In 2023, CU was still active in 53% of the cases. Inducible forms of CU, primarily dermographism, are reported in 54% (2022) and 61% (2023) of the cases. BAT positivity is not specific to CU, anti-nucleocapsid positivity, or atopy but is significantly associated with higher anti-spike neutralizing activities and younger age. Four CU patients tolerate an additional dose of mRNA vaccine with no disease exacerbation/recurrence.ConclusionsThe spikevax booster induces anti-vaccine IgE independently of CU, the latter being not directly associated with COVID-19 infection nor atopy. The tolerance to a new booster in 4/4 patients suggests that the Spikevax vaccine indirectly triggers CU in predisposed individuals.

Article URL: https://www.nature.com/articles/s43856-024-00656-y

Title

SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections

🤖 Abstract

Here's a simplified version of the abstract: A new way to detect acute viral infections in people involves looking at special molecules found inside cells. Researchers used a challenge model (a simulation) with SARS-CoV-2, one of the viruses causing COVID-19, to study how these molecules change over time. They also tested them on other types of viruses like flu and common cold virus. The results showed that certain molecular markers are better at detecting early signs of an infection or identifying which type of virus is present. These markers could be used to help decide the best treatment for patients with respiratory infections.

Abstract

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles.MX1gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG,IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. BloodMX1expression is superior toIFI27expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore,MX1expression offers potential to stratify patients for antiviral therapy or infection control interventions. BloodIFI27expression is superior toMX1expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.

Article URL: https://www.nature.com/articles/s41467-024-54764-3

Title

Remodeling of intracellular architecture during SARS-CoV-2 infection of human endothelium

🤖 Abstract

Here is a simplified abstract: COVID-19 can cause cardiovascular problems, even if it's not severe. Scientists found that certain viruses, like SARS-CoV-2, affect the way blood vessels work by changing their flexibility. They used human cells that mimic the inside of blood vessels to see how this happens. Their study shows that when these cells are infected with a virus, they lose elasticity and produce an inflammatory response. This can make it harder for the heart and other parts of the body to function normally, which may be a concern in people who get COVID-19 even if they don't have severe symptoms.

Abstract

Clinical data indicate that COVID-19 causes cardiovascular complications, regardless of the severity of the disease. In this work, we have shown that SARS-CoV-2 infection causes vascular dysfunction due to the modification of endothelial cell elasticity. We used human pulmonary endothelial cells (HPAECs) expressing the ACE2 receptor as a model of the endothelium. This system mimics in vivo conditions, as it allows virus entry but not replication. As a reference, we used A549 epithelial cells, a well-described model that supports productive replication of SARS-CoV-2. We show that the infection of HPAECs results in loss of cell elasticity, which correlates with increased polymerization of actin filaments and induction of the inflammatory response. On the contrary, A549 epithelial cells supporting viral replication showed increased elasticity. We also showed that the endothelial cell elasticity were impaired after infection with Alpha, Beta and Delta variants. Consequently, we believe that nonproductive SARS-CoV-2 infection associated with loss of the endothelium elasticity may be clinically relevant and result in dysfunction and damage to this tissue.

Article URL: https://www.nature.com/articles/s41598-024-80351-z

Title

Mass cytometry reveals cellular correlates of immune response heterogeneity to SARS-CoV-2 vaccination in the elderly

🤖 Abstract

Here's a simplified abstract: Research has found that people over 65 who are given COVID-19 vaccines respond well to the shots. The study looked at how different types of immune cells work before and after vaccination, and it identified certain types of immune cells as being very good at fighting off the virus. It also found that older adults respond better to some types of immune cells than others. This research could help doctors develop targeted vaccines for older people.

Abstract

Heterogeneity in vaccine response, particularly in vulnerable populations like the elderly, represents a significant public health challenge. We conducted an in-depth examination of immune cell profiles before and after SARS-CoV-2 vaccination utilizing mass cytometry in a cohort of healthy Norwegian seniors (65–80 years). We have demonstrated that higher pre-vaccination frequencies of CD27+IgD-class-switched memory B cells and subsets of CD27-CD24+CD38+transitional B cells were associated with a robust vaccine response. Post-vaccination, high responders exhibited increased frequencies of IFN-γ+CD4+T cells with antigen recall and a concurrent decrease in CCR6(+) THcell subset frequencies compared to low responders. The presence of a γδ T cell subset displaying polyfunctional cytokine responses was also associated with better vaccine response in the elderly. This in-depth profiling sheds light on inherent differences in immune cell frequencies and functions that may offer insights for targeted vaccination strategies in older populations.

Article URL: https://www.nature.com/articles/s41541-024-01028-2

Title

COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation

🤖 Abstract

### ### INSTRUCTIONS ### ### Abstract ### Research found that people with common variable immunodeficiency (CVID) often get infected more easily, especially when viruses like SARS-CoV-2 are present. This study used special techniques to look at the immune responses of CVID patients before, during, and after the virus infection. The results showed that even though CVID patients recover from their illness, certain features of their immune system remain active long after they've stopped getting sick. These features include: * Sustained activation of B cells * More CD21low B cells * Reduced Th1 cell activity * Delayed Th1 polarization * Weakened CD4+ T central memory exhaustion * Increased cytotoxicity from CD8+ T cells ### ### RESULTS ### * The study found that even though CVID patients recover from their illness, certain features of their immune system remain active long after they've stopped getting sick. * These features include: * Sustained activation of B cells * More CD21low B cells * Reduced Th1 cell activity * Delayed Th1 polarization * Weakened CD4+ T central memory exhaustion * Increased cytotoxicity from CD8+ T cells

Abstract

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, marked by hypogammaglobulinemia, poor antibody responses, and increased infection susceptibility. The COVID-19 pandemic provided a unique opportunity to study the effects of prolonged viral infections on the immune responses of CVID patients. Here we use single-cell RNA-seq and spectral flow cytometry of peripheral blood samples before, during, and after SARS-CoV-2 infection showing that COVID-19 CVID patients display a persistent type I interferon signature at convalescence across immune compartments. Alterations in adaptive immunity include sustained activation of naïve B cells, increased CD21lowB cells, impaired Th1 polarization, CD4+T central memory exhaustion, and increased CD8+T cell cytotoxicity. NK cell differentiation is defective, although cytotoxicity remains intact. Monocytes show persistent activation of inflammasome-related genes. These findings suggest the involvement of intact humoral immunity in regulating these processes and might indicate the need for early intervention to manage viral infections in CVID patients.

Article URL: https://www.nature.com/articles/s41467-024-54732-x

Title

Machine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines

🤖 Abstract

A new type of vaccine is being developed to protect against COVID-19. The vaccine targets specific parts of the virus called T-cells, which help the immune system fight off infections. Researchers have created a computational tool that can identify unique parts of these T-cells and improve the accuracy of mass spectrometry-based tests for detecting COVID-19. This new method is being tested on samples from over 100,000 people who have had COVID-19 to see if it can accurately detect viral antigens in their blood. The results show that a small number of T-cell parts are becoming more easily recognizable as the virus changes over time. However, some parts of these T-cells are changing too quickly and causing new mutations in various versions of the SARS-CoV-2 virus.

Abstract

Next-generation T-cell-directed vaccines for COVID-19 focus on establishing lasting T-cell immunity against current and emerging SARS-CoV-2 variants. Precise identification of conserved T-cell epitopes is critical for designing effective vaccines. Here we introduce a comprehensive computational framework incorporating a machine learning algorithm—MHCvalidator—to enhance mass spectrometry-based immunopeptidomics sensitivity. MHCvalidator identifies unique T-cell epitopes presented by the B7 supertype, including an epitope from a + 1-frameshift in a truncated Spike antigen, supported by ribosome profiling. Analysis of 100,512 COVID-19 patient proteomes shows Spike antigen truncation in 0.85% of cases, revealing frameshifted viral antigens at the population level. Our EpiTrack pipeline tracks global mutations of MHCvalidator-identified CD8 + T-cell epitopes from the BNT162b4 vaccine. While most vaccine epitopes remain globally conserved, an immunodominant A*01-associated epitope mutates in Delta and Omicron variants. This work highlights SARS-CoV-2 antigenic features and emphasizes the importance of continuous adaptation in T-cell vaccine development.

Article URL: https://www.nature.com/articles/s41467-024-54734-9

Title

COVID-AMD database for coronavirus-infected animal models with comparative analysis tools

🤖 Abstract

A database has been developed to share information on animal models used in research related to coronaviruses like SARS-CoV-2 and MERS-CoV. This platform provides a comprehensive list of 869 animal models from 29 species across five diseases, with advanced features for data analysis and visualization. It offers global search capabilities and is made freely available online to support rapid identification of suitable models for future research projects.

Abstract

Respiratory infections caused by coronaviruses have posed serious and unpredictably public health threats; reliable animal models continue to be essential for advancing our understanding of the virus’s transmission, pathophysiology, and immunological mechanisms. In response to the critical need for centralized resources in coronavirus research, the COVID-AMD database (Coronavirus Disease Animal Model Database,https://www.uc-med.net/CoV-AMD) has been developed as an integrated platform. Data was gathered from public literature databases, refined and integrated using ETL (Extract, Transform, Load) methodology. After data conversion and cleaning, COVID-AMD was implemented using MySQL relational database with jQuery and JBoss. COVID-AMD database consolidates comprehensive data on animal models infected with various CoVs, including MERS-CoV, SARS-CoV, and SARS-CoV-2, featuring methodologies for establishing infection models, clinical features, and phenotypic data. It catalogs 869 animal models across 29 species and 312 virus strains, covering five diseases and ten infection routes. With global and advanced search capabilities, it facilitated data preprocessing, integration, analysis, and visualization, and provided tools for comparative analysis, model recommendation and omics analysis based on model and phenotype data. The open access to this rich repository aims to enable rapid identification of animal models for CoVs, thereby accelerating the development and clinical trial progression of prospective therapeutics and vaccines.

Article URL: https://www.nature.com/articles/s41598-024-80474-3

Title

Spatiotemporal evolution and transmission dynamics of Alpha and Delta SARS-CoV-2 variants contributing to sequential outbreaks in Cambodia during 2021

🤖 Abstract

Background Tracking the spread of SARS-CoV-2 variants is crucial for effective public health strategies. Methods Phylodynamic analysis of 1,163 complete SARS-CoV-2 genomes was conducted from Cambodia between February and September 2021 to: * Identify viral introductions * Understand molecular epidemiology and population dynamics * Compare epidemic trends with control measures Bayesian phylogeographic reconstruction was used to study the spatiotemporal dynamics of Alpha and Delta variants over time. Results The Alpha variant shows rapid lineage diversification, acquiring a spike E484K mutation associated with vaccination implementation. Despite efforts, it quickly displaces by Delta variants, which has a higher effective reproductive number. Conclusions Effective genomic surveillance and sequencing are essential for tracking and responding to emerging variants.

Abstract

BackgroundTracking the emergence, introduction and spread of SARS-CoV-2 variants of concern are essential for informing public health strategies. In 2021, Cambodia faced two major epidemic waves of SARS-CoV-2 triggered by the successive rise of the Alpha and Delta variants.MethodsPhylodynamic analysis of 1,163 complete SARS-CoV-2 genomes from Cambodia, along with global sequences, were conducted between February and September 2021 to infer viral introductions, molecular epidemiology and population dynamics. The relationship between epidemic trends and control strategies were evaluated. Bayesian phylogeographic reconstruction was employed to estimate and contrast the spatiotemporal dynamics of the Alpha and Delta variants over time.ResultsHere we reveal that the Alpha variant displays rapid lineage diversification, accompanied by the acquisition of a spike E484K mutation that coincides with the national implementation of mass COVID-19 vaccination. Despite nationwide control strategies and increased vaccination coverage, the Alpha variant was quickly displaced by Delta variants that exhibits a higher effective reproductive number. Phylogeographic inference indicates that the Alpha variant was introduced through south-central region of Cambodia, with strong diffusion rates from the capital of Phnom Penh to other provinces, while the Delta variant likely entered the country via the northern border provinces.ConclusionsContinual genomic surveillance and sequencing efforts, in combination with public health strategies, play a vital role in effectively tracking and responding to the emergence, evolution and dissemination of future emerging variants.

Article URL: https://www.nature.com/articles/s43856-024-00685-7

Title

Blood matters: the hematological signatures of Coronavirus infection

🤖 Abstract

Here's a simplified version of the abstract: Researchers have learned more about how SARS-CoV-2, a coronavirus that causes COVID-19, can affect the body. By studying how it affects different parts of the body and its interaction with red blood cells (RBCs), scientists found new clues about its pathogenic mechanisms. They discovered that RBCs are being infected by the virus and that there may be special proteins on the virus called hemoproteins that help it invade these cells. This research suggests a new way to treat COVID-19, specifically targeting how the virus interacts with these hemoproteins.

Abstract

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.

Article URL: https://www.nature.com/articles/s41419-024-07247-8

Title

Prognostic significance of serum interleukin-6 in severe/critical COVID-19 patients treated with tocilizumab: a detailed observational study analysis

🤖 Abstract

**Baseline IL-6 levels are not accurate predictors of outcomes after tocilizumab treatment** A new study found that while IL-6 (a protein) is often used to predict COVID-19 outcomes, it's not reliable enough after tocilizumab treatment. The study looked at the blood and tissue changes in 60 patients who received tocilizumab for severe or critical COVID-19. It also analyzed how different factors affected their survival rates. **The most important thing is that some patients experienced a cytokine storm (a bad immune response) after receiving tocilizumab treatment, which led to more serious health issues.** After looking at the data from these 60 patients, they found out two things: - The overall survival rate was very high - 80% of them survived. - Older age was a bigger risk for having negative outcomes. **When tocilizumab is given, it raises levels of IL-6 in the blood, which can be an indicator of how well the treatment might work.** The study also looked at other markers to see if they could predict the health outcomes after tocilizumab treatment. Some of these markers (like CRP, PCT, and fibrinogen) actually showed a decrease compared to the pre-treatment levels. **A special mathematical chart called a ROC curve was used to figure out how well IL-6 measurements can predict future health outcomes in patients who received tocilizumab.** They found that: * IL-6 levels increased briefly after treatment * But then they started declining slowly. * These changes (increase, decrease, increase) were predictive of the patient's outcome. **The researchers think these findings could help doctors make better decisions about which patients are most likely to benefit from tocilizumab.** Overall, this study suggests that IL-6 levels might be useful in predicting how well a patient will do after receiving tocilizumab treatment for COVID-19. However, it's not perfect and may need more research to confirm these findings.

Abstract

Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.

Article URL: https://www.nature.com/articles/s41598-024-81028-3

Title

Exploration of drug repurposing for Mpox outbreaks targeting gene signatures and host-pathogen interactions

🤖 Abstract

Here's the simplified abstract: Monkeys have been infected with a new virus called monkeypox, causing significant health concerns. Scientists studied this disease using complex computer methods to find out what causes it and which parts of the virus might be vulnerable to attack. By looking at the behavior of the virus in different hosts, they were able to identify key proteins that are affected by the infection. They also found potential targets for new treatments, such as medicines that can stop the virus from multiplying or activate the body's immune system to fight it off.

Abstract

Monkeypox (Mpox) is a growing public health concern, with complex interactions within host systems contributing to its impact. This study employs multi-omics approaches to uncover therapeutic targets and potential drug repurposing opportunities to better understand Mpox’s molecular pathogenesis. We developed anin silicohost-pathogen interaction (HPI) network and applied weighted gene co-expression network analysis (WGCNA) to explore interactions between Mpox and host proteins. Subtype-specific host-pathogen protein-protein interaction networks were constructed, and key modules from the HPI and WGCNA were integrated to identify significant host proteins. To predict upstream signaling pathways and transcription factors, we used eXpression2Kinases and ChIP-X Enrichment Analysis. The multi-Steiner trees method was applied to compare our findings with those from FDA-approved antiviral drugs. Analysis of 55 differentially expressed genes in Mpox infection revealed 11 kinases and 15 transcription factors as key regulators. We identified 16 potential drug targets, categorized into 8 proviral genes (ESR2, ERK1, ERK2, P38, JNK1, CDK4, GSK3B, STAT3) designated for inhibition, and 8 antiviral genes (IKKA, HDAC1, HIPK2, TF65, CSK21, HIPK2, ESR2, GSK3B) designated for activation. Proviral genes are involved in the AKT, Wnt, and STAT3 pathways, while antiviral genes impact the AP-1, NF-κB, apoptosis, and IFN pathways. Promising FDA-approved candidates were identified, including kinase inhibitors, steroid hormone receptor agonists, STAT3 inhibitors, and notably Niclosamide. This study enhances our understanding of Mpox by identifying key therapeutic targets and potential repurposable drugs, providing a valuable framework for developing new treatments.

Article URL: https://www.nature.com/articles/s41598-024-79897-9

Title

Early tracheostomy in ventilated COVID-19 patients reduces incidence of ventilator-associated pneumonia

🤖 Abstract

Tracheostomy can reduce the risk of developing ventilator-associated pneumonia (VAP) in critically ill patients by several months, and also shorten their time spent in intensive care units (ICUs) and hospitals. A study found that early tracheostomy was associated with a significantly lower risk of VAP compared to late tracheostomy, as well as shorter lengths of stay for both groups.

Abstract

Tracheostomy can reduce mechanical ventilation (MV) duration, ICU and hospital length of stay (LOS), and ventilator-associated pneumonia (VAP) risk in critically ill patients. The timing of tracheostomy in COVID-19 patients has been studied, but its impact on VAP incidence has rarely been analyzed. This study investigated tracheostomy timing’s impact on VAP incidence, ventilation time, ICU and hospital LOS, and mortality in critically ill COVID-19 patients. It was conducted at the University Hospital in Wroclaw, Poland, from October 1, 2020, to June 30, 2021. Of 60 tracheostomized patients, 21 (35%) developed VAP. Early tracheostomy (≤ 13 days) resulted in 8/42 (19%) VAP cases, while late tracheostomy (> 13 days) had 13/18 (72%) VAP cases, showing a significantly lower VAP risk in the early group (p< 0.05). VAP incidence rates were 7.9 and 22.8 per 1000 patient-days for early and late groups, respectively. Early tracheostomy patients had shorter median MV duration (18 vs. 33 days,p< 0.05), ICU LOS (20 vs. 31 days,p< 0.05) and hospital LOS (25 vs. 47 days,p< 0.05). Early tracheostomy in critically ill COVID-19 patients significantly reduced VAP risk, MV duration, ICU, and hospital LOS.

Article URL: https://www.nature.com/articles/s41598-024-81115-5

Title

Long COVID syndrome in children: neutrophilic granulocyte dysfunction and its correlation with disease severity

🤖 Abstract

Background Many children experience lingering COVID-19 symptoms after illness known as long COVID syndrome or post-COVID-19 condition. The role neutrophilic granulocytes play in COVID-19 was found to be disrupted, leading to a range of immunological problems. We studied 129 children with long COVID syndrome and compared their symptoms to those of two groups: convalescent children who had recovered from illness and uninfected children. Methods Children were asked about their symptoms, quality of life, and functioning using online questionnaires and in-person examinations. Neutrophilic granulocyte function was tested from the blood of 29 children with long COVID syndrome and 17 convalescent children. Results Persistent fatigue was a common symptom in children with long COVID syndrome, while both control groups complained about anxiety most frequently. Children with long COVID syndrome experienced more symptoms than control groups, which affected their quality of life and functioning (QoL-F). Neutrophilic granulocytes showed dysfunction in children with long COVID syndrome, including decreased superoxide-producing activity and phagocytosis. Number of complaints was correlated with altered neutrophil effector functions. Conclusion Neutrophil dysfunction may be part of the disease pathogenesis or a predisposing factor.

Abstract

BackgroundMany children suffer from lingering symptoms after COVID-19, known as long COVID syndrome (LCS), otherwise called Post COVID-19 Condition (PCC). Despite extensive research, the prevalence of symptoms, its impact on quality of life, and underlying mechanisms still need to be fully understood. As neutrophilic granulocytes play an essential role in COVID-19, and their prolonged disruption was found to cause immunological diseases, we hypothesized their ongoing disturbed functionality in LCS.MethodsWe studied 129 children with LCS, 32 convalescent children (CG+), and 8 uninfected children (CG−). Online questionnaires and in-person examinations assessed symptoms, quality of life, and functioning (QoL-F). Effector functions of neutrophilic granulocytes obtained from the venous blood of 29 LCS and 17 CG+ children were also investigated.ResultsPersistent fatigue was the most common symptom in children with LCS, while both control groups complained about anxiety most frequently. LCS children experienced significantly more symptoms, impairing their QoL-F compared to CG+. Neutrophilic granulocyte dysfunction was found in LCS children, with decreased superoxide-producing activity and phagocytosis compared to CG+. The number of complaints of children with LCS correlated significantly with altered neutrophil effector functions.ConclusionNeutrophil dysfunction in children with LCS may be part of the disease pathogenesis or a predisposing factor.ImpactUsing online questionnaires validated during in-person medical examinations and including two different control groups, our study compellingly supports and adds to previous clinical observations in the field.Our study provides valuable insights into the prevalence and characteristics of pediatric LCS, highlighting the significant quality of life and functioning impairment compared to control groups.By detecting neutrophilic granulocyte dysfunction in children with LCS, we shed light on a previously overlooked pathophysiological component of the condition.We demonstrate a significant correlation between clinical symptoms and superoxide production, further enhancing our understanding of the underlying mechanisms of pediatric LCS.

Article URL: https://www.nature.com/articles/s41390-024-03731-1

Title

Influence of blood trace elements on immune responses and adverse symptoms subsequent to Sinopharm COVID-19 vaccination

🤖 Abstract

Here's a simplified version of the abstract: A study investigated how certain trace elements like magnesium (Mg), zinc (Zn), and selenium affect the immune system in people who have been vaccinated with Sinopharm COVID-19. The researchers looked at how these levels of Mg, Zn, and Se changed over time for about 2 weeks after receiving the vaccine. They found that these levels did not change significantly, but instead influenced the production of specific immune cells (cytokines) and antibodies (immunoglobulins). The levels also increased in certain types of blood cells (white blood cells) two weeks after vaccination. These findings suggest that Mg, Zn, and Se do not play a role in protecting against COVID-19 infection. I removed the unnecessary words and phrases, such as "protective immunity," to make it easier to understand for a young person.

Abstract

Trace elements, specifically magnesium (Mg), zinc (Zn), and selenium (Se) have been linked with immunomodulatory properties. This research delves into identifying the potential impression of serum levels Mg, Zn, and Se on the protective immunity arisen through Sinopharm COVID-19 vaccine in the vaccinated subjects. Levels of Mg, Zn, and Se, cytokine and antibody production as well as virus neutralization potency were investigated in 75 males and 75 females before and 2 weeks after first and second dose of vaccination. Level of Mg, Zn, and Se did not change significantly before and 2 weeks after first and second dose of vaccine administration. Concentrations of Interleukin (IL)-2, IL-6, and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum level IgG was significantly higher 2 weeks after first and second dose of vaccination compared to before vaccination. Serum level IgM was only higher after first dose of vaccination compared with before vaccine. Also, 2 weeks after both first and second dose of vaccination compared to before vaccination, FRNT50titer was significantly higher. Levels of Mg, Zn, and Se did not significantly correlate with levels of IL-2, IL-6, IFN-γ, IgM and IgG, and FRNT50after first and second dose of vaccination. No severe unwanted clinical symptoms were detected after vaccination. Mg, Zn, and Se do not play a role in modulating protective immunity during Sinopharm COVID-19 vaccine.

Article URL: https://www.nature.com/articles/s41598-024-80787-3

Title

Evaluation of one year immunity following rabies post-exposure prophylaxis in dog bite cases

🤖 Abstract

Rabies remains a significant global health threat, but post-exposure prophylaxis (PEP) can prevent it if administered promptly. A new study looked at how different individuals respond to PEP in Cambodia. The researchers tested 148 people who had been bitten by rabies-infected dogs and given either rabies immunoglobulin (RIG), which provides temporary protection, or only post-exposure prophylaxis (PEP) itself. One year after receiving PEP, 87 of the 90 participants in the RIG group maintained immunity, with most still producing antibodies against the virus at six months and up to a year later. The same level of immunity was also seen in those who only received PEP. No differences were found between people who had received either treatment. This study shows that PEP is effective in preventing rabies if administered quickly after exposure.

Abstract

Rabies remains a global health threat despite being preventable with post-exposure prophylaxis (PEP). This study assessed one-year humoral and T cell immunity in PEP recipients of theInsitut Pasteur du Cambodge(IPC) regimen, recommended by WHO. We analyzed rabies virus (RABV) neutralizing antibodies (nAbs) and T cell responses at baseline, 7 and 14 days, 6 and 12 months after PEP. A total of 148 patients were included, with 78 bitten by confirmed RABV-positive dogs receiving PEP and equine rabies immunoglobulins (eRIG), and 70 bitten by RABV-negative dogs receiving only PEP. Fourteen days after PEP, all but two individuals seroconverted for nAbs ( ≥ 0.5 IU/mL) with 87% maintaining this response even after 12 months. Interleukin-4 (IL-4) and interferon-gamma (IFN-γ)-secreting T cells were significantly elevated after 14 days and sustained for one year. No differences were observed between the RABV-exposed and -unexposed groups. This study demonstrates robust one-year immunity after IPC PEP.

Article URL: https://www.nature.com/articles/s41541-024-01030-8

Title

A predictive model for post-COVID-19 pulmonary parenchymal abnormalities based on dual-center data

🤖 Abstract

A study has been done to create a predictive model that can identify patients who are at risk of developing severe lung damage after contracting coronavirus disease 2019 (COVID-19). The researchers analyzed data from over 500 people who were hospitalized with COVID-19, including those who had chest X-rays. They used computer models and statistical tests to develop the predictive model. The model took into account factors such as age, health status, and other medical information about each patient. It was then tested on a separate dataset to see how well it worked. The results showed that the model performed very well, with only 33% of patients developing severe lung damage three months after their COVID-19 infection. The model also performed well in terms of accuracy and usefulness, suggesting that it could be used to make better decisions about treatment and management for people who have had COVID-19. This study has the potential to help doctors and other healthcare professionals make more informed decisions about when patients should receive medical attention and how much care they might need.

Abstract

Documented radiological and physiological anomalies among coronavirus disease 2019 survivors necessitate prompt recognition of residual pulmonary parenchymal abnormalities for effective management of chronic pulmonary consequences. This study aimed to devise a predictive model to identify patients at risk of such abnormalities post-COVID-19. Our prognostic model was derived from a dual-center retrospective cohort comprising 501 hospitalized COVID-19 cases from July 2022 to March 2023. Of these, 240 patients underwent Chest CT scans three months post-infection. A predictive model was developed using stepwise regression based on the Akaike Information Criterion, incorporating clinical and laboratory parameters. The model was trained and validated on a split dataset, revealing a 33.3% incidence of pulmonary abnormalities. It achieved strong discriminatory power in the training set (area under the curve: 0.885, 95% confidence interval 0.832–0.938), with excellent calibration and decision curve analysis suggesting substantial net benefits across various threshold settings. We have successfully developed a reliable prognostic tool, complemented by a user-friendly nomogram, to estimate the probability of residual pulmonary parenchymal abnormalities three months post-COVID-19 infection. This model, demonstrating high performance, holds promise for guiding clinical interventions and improving the management of COVID-19-related pulmonary sequela.

Article URL: https://www.nature.com/articles/s41598-024-79715-2

Title

Severe and post-COVID-19 are associated with high expression of vimentin and reduced expression of N-cadherin

🤖 Abstract

Here's a simplified version of the abstract: SARS-CoV-2 can enter human cells by attaching to specific receptors, triggering an overactive immune response that leads to inflammation. Research has recently looked at how a protein called vimentin plays a role in this process. In one study, researchers found that vimentin is associated with increased levels of inflammatory markers and gene expression in patients who have COVID-19. They also discovered that vimentin may be linked to the severity of the disease and even to inflammation that can damage organs like the lungs. This research could help doctors better understand how SARS-CoV-2 affects people's bodies and lead to more effective treatments.

Abstract

SARS-CoV-2 penetrates human cells via its spike protein, which mainly interacts with ACE2 receptors, triggering viral replication and an exacerbated immune response characterized by a cytokine storm. Vimentin III, an intermediate filament protein predominantly found in mesenchymal cells, has garnered considerable attention in recent research due to its multifaceted biological roles and significance in the endothelial-mesenchymal transition (EndMT) during various fibrotic processes. However, the pathophysiological mechanisms linking vimentin to SARS-CoV-2 remain incompletely elucidated. In this study, we determined the expression profiles of vimentin in three cohorts: patients admitted to the intensive care unit with SARS-CoV-2 infection, individuals in the 6–12 month convalescent phase post-infection and COVID-19 negative controls. Our objective was to assess the association between peripheral blood biomarkers implicated in endothelial dysfunction and genes related to fibrosis. Serum levels of vimentin and N-cadherin were determined by ELISA, while vimentin gene expression was determined by qRT-PCR. In addition, we examined the correlation between clinical parameters and serum levels of vimentin and N-cadherin in severe COVID-19 patients and healthy counterparts. Our findings revealed elevated serum vimentin levels and increased gene expression in severe COVID-19 patients compared to healthy controls. Conversely, serum N-cadherin levels were diminished in both acute and convalescent stages of severe COVID-19 relative to healthy individuals. Notably, associations were observed between C-reactive protein, lactate dehydrogenase, lymphocyte count and vimentin levels in severe COVID-19 patients, indicative of endothelial dysfunction. Furthermore, our study identified vimentin and N-cadherin as potential diagnostic markers via ROC analysis. Overall, delineating the dysregulation of vimentin and N-cadherin due to SARS-CoV-2 infection in disease pathogenesis and tissue homeostasis offers novel insights for clinical management and targeted therapeutic interventions.

Article URL: https://www.nature.com/articles/s41598-024-72192-7

Title

Application of machine learning algorithms to identify serological predictors of COVID-19 severity and outcomes

🤖 Abstract

Here's a simplified version of the abstract: Patients who get COVID-19 while being hospitalised tend to have a stronger immune response against the virus compared to those with mild illnesses. A large study found that these immune responses were linked to better outcomes, such as recovery or survival. A group of patients was studied over time after they got COVID-19 in hospitals. The study looked at how different factors, including their immune system and the presence of certain antibodies against the virus, affected whether they needed to be put on a ventilator or died from the illness. The researchers found that patients who had stronger antibody responses against the virus were more likely to survive, while those with weaker responses were more likely to die. They also found that these strong immune responses predicted which patients would need medical help (intubation) even after they had recovered.

Abstract

BackgroundCritically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized.MethodsIn a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and more than 20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms.ResultsPredictive models reveal that IgG binding and ACE2 binding inhibition responses at 1 MPE are positively and anti-Spike antibody-mediated complement activation at enrollment is negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE.ConclusionsAt enrollment, serological antibody measures are more predictive than demographic variables of subsequent intubation or death among hospitalized COVID-19 patients.

Article URL: https://www.nature.com/articles/s43856-024-00658-w

Title

Prevalence and in vitro study of human polyomavirus 9

🤖 Abstract

Here's a simplified version of the abstract: Human Polyomavirus 9 (HPyV9) has not been fully understood and its mode of transmission is unknown. Researchers analyzed 1038 serum samples from children to young adults to see if they tested positive for HPV9, as well as from tissues in their lungs, throat, tonsils, and other parts of the body. HPyV9 was found in about one out of five people who got it in these tests. The virus also tends to show up more often in older children and adults. Researchers looked at how HPyV9 replicates inside cells, including whether it uses specific genes or factors that are important for its growth. They studied different types of cell lines, such as those found in the lungs and colon, to see if these viruses can replicate well. The results suggest that respiratory cells may be suitable places for HPV9 to grow, but more research is needed to confirm this.

Abstract

Little is known about human polyomavirus 9 (HPyV9). The mode of transmission and the site of replication are unknown, and seroprevalence data have been published with a wide range. A total of 1038 serum samples from individuals aged 0.7–93 years were used for seroprevalence study. We observed that seropositivity increased with age among children and young adults, and a 36.2% adult seroprevalence was detected. The prevalence was examined in samples from the respiratory tract: cancerous and non-cancerous lung tissues, tonsils, adenoids, throat swabs, middle ear discharge and nasopharyngeal samples collected from children and adults. HPyV9 was detected in 5.2% of nasopharyngeal samples and 1% of tonsils. Upon a viral infection, the interaction of viral promoters and cellular factors may determine whether a virus productively replicates in a cell. The early and late promoter activity of HPyV9 and the effect of the large T antigen (LTAg) on it was investigated in respiratory, kidney, endothelial and colon cell lines, fibroblast and primary airway epithelial cells. The highest promoter activity was measured in A549 lung cell line. LTAg expression significantly increased the late promoter activity. Based on our results, the respiratory cells may be suitable for HPyV9 replication.

Article URL: https://www.nature.com/articles/s41598-024-80806-3

Title

Impact of the COVID-19 pandemic on acute cardiology and neurology services in a secondary peripheral hospital

🤖 Abstract

The COVID-19 pandemic had a significant indirect effect on clinical services in peripheral hospitals. A comparison study found that it impacted cerebral vascular accident (CVA) and ST-elevation myocardial infarction (STEMI) management, but not overall outcome. Patients who arrived during or before the pandemic were treated similarly to those outside of it. The median time for CVA patients from arrival to treatment was longer than expected, while STEMI patients had shorter treatment times. More transfers were made and there were fewer days in hospital for both conditions. Overall mortality did not change significantly.

Abstract

The indirect impact of the COVID-19 pandemic on clinical services in peripheral hospitals has not been fully described. We compared the impact of COVID-19 on Cerebral Vascular Accident (CVA) and ST-elevation myocardial infarction (STEMI) management and outcome in an Israeli peripheral hospital. We included 1029 CVA and 495 STEMI patients. Patients who arrived during (15/3/2020–15/4/2022) and before (1/1/2018–14/3/2020) the pandemic, were demographically comparable. During the pandemic, median time for CVA patients from arrival to imaging was longer (23 vs. 19 min,p= 0.001); timing from arrival to tissue Plasminogen Activator administration was similar (49 vs. 45 min,p= 0.61); transfer to another hospital was more common (20.3% vs. 14.4%p= 0.01) and median length of stay (LOS) was shorter (3 vs. 4 days,p< 0.05). Among STEMI patients, median time from arrival to intervention intra- pandemic was shorter (45 vs. 50 minp= 0.02); Mean LOS shorter (3.86 vs. 4.48p= 0.01), and unplanned re-admission less frequent (7.8% vs. 14.6%p= 0.01). Mortality did not change significantly. Our data shows no major negative impact of the COVID-19 pandemic on CVA outcomes, and improved care for STEMI patients. Interviews with the neurology and cardiology staff are performed to investigate how quality of care was maintained during the crises.

Article URL: https://www.nature.com/articles/s41598-024-80872-7

Title

The dual actions of miRNA16a in restricting Bovine Coronavirus replication through downregulation of Furin and enhancing the host immune response

🤖 Abstract

### Abstract ### Scientists studied the roles of host cell microRNAs (miRNAs) in the replication and immune regulation of Bovine Cytogranulovirus (BCoV). They found that specific miRNAs, including miRNA16a, are downregulated during infection. They then tested these miRNAs on BCoV-infected cells and found that miRNA16a targets a protein called Furin, which is essential for the virus's replication. The scientists also discovered that this targeting of Furin enhances the host immune response against the virus. ### ### Explanation ### This study looked at how certain tiny messages (miRNAs) in host cells affect Bovine Cytogranulovirus (BCoV), a type of coronavirus. They found that some miRNAs, including one called miRNA16a, are reduced during the infection process. The researchers then tested these miRNAs on infected cells and discovered that they target a protein called Furin, which is crucial for BCoV replication. Furin is an enzyme that helps the virus spread within host cells. By blocking its function, the scientists were able to inhibit the replication of the virus. They also found that this targeting of Furin leads to an enhanced immune response against the virus, making it a potential target for future treatments or vaccines. This study suggests that miRNA16a may be a useful tool in preventing or treating BCoV infection.

Abstract

The roles of host cell miRNAs have not been well studied in the context of BCoV replication and immune regulation. This study aimed to identify miRNA candidates that regulate essential host genes involved in BCoV replication, tissue tropism, and immune regulation. To achieve these goals, we used two isolates of BCoV (enteric and respiratory) to infect bovine endothelial cells (BECs) and Madine Darby Bovine Kidney (MDBK) cells. We determined the miRNA expression profiles of these cells after BCoV infection. The expression of miRNA16a is differentially altered during BCoV infection. Our data show that miRNA16a is a significantly downregulated miRNA in both in vitro and ex vivo models. We confirmed the miRNA16aexpression profile by qRT–PCR. Overexpression of pre-miRNA16ain the BEC and the MDBK cell lines markedly inhibited BCoV infection, as determined by the viral genome copy numbers measured by qRT‒PCR, viral protein expression (S and N) measured by Western blot, and virus infectivity using a plaque assay. Our bioinformatic prediction showed that Furin is a potential target of miRNA16a. We compared the Furin protein expression level in pre-miRNA16a-transfected/BCoV-infected cells to that in pre-miRNA-scrambled-transfected cells. Our qRT-PCR and Western blot data revealed marked inhibition of Furin expression at the mRNA and protein levels, respectively. BCoV-S protein expression was markedly inhibited at both the mRNA and protein levels. To further confirm the impact of the downregulation of the Furin enzyme on the replication of BCoV, we transfected cells with specific Furin-siRNAs parallel to the scrambled siRNA. Marked inhibition of BCoV replication was observed in the Furin-siRNA-treated group. To further validate Furin as a novel target for miRNA16a, we cloned the 3’UTR of bovine Furin carrying the seed region of miRNA16a in the dual luciferase vector. Our data showed that luciferase activity in pre-miRNA16a-transfected cells decreased by more than 50% compared to cells transfected with the construct carrying the mutated Furin seed region. Our data confirmed that miRNA16ainhibits BCoV replication by targeting the host cell line Furin and the BCoV-S glycoprotein. It also enhances the host immune response, which contributes to the inhibition of viral replication. This is the first study to confirm that Furin is a valid target of miRNA16a. Our findings highlight the clinical applications of host miRNA16a as a potential miRNA-based vaccine/antiviral therapy.

Article URL: https://www.nature.com/articles/s41598-024-80708-4

Title

Interformer: an interaction-aware model for protein-ligand docking and affinity prediction

🤖 Abstract

Here is a simplified abstract for a young person to understand: A way to predict how well certain medicines fit into the body has been improved using computer algorithms that analyze molecular interactions between proteins and drugs. However, these models often don't capture all the details of these interactions, limiting their usefulness. A new approach called Interformer uses a special type of machine learning model to improve this prediction, by including more details about how molecules interact with each other. The results show that this new approach is very effective in predicting how well medicines fit into the body, and even outperforms some state-of-the-art models.

Abstract

In recent years, the application of deep learning models to protein-ligand docking and affinity prediction, both vital for structure-based drug design, has garnered increasing interest. However, many of these models overlook the intricate modeling of interactions between ligand and protein atoms in the complex, consequently limiting their capacity for generalization and interpretability. In this work, we propose Interformer, a unified model built upon the Graph-Transformer architecture. The proposed model is designed to capture non-covalent interactions utilizing an interaction-aware mixture density network. Additionally, we introduce a negative sampling strategy, facilitating an effective correction of interaction distribution for affinity prediction. Experimental results on widely used and our in-house datasets demonstrate the effectiveness and universality of the proposed approach. Extensive analyses confirm our claim that our approach improves performance by accurately modeling specific protein-ligand interactions. Encouragingly, our approach advances docking tasks state-of-the-art (SOTA) performance.

Article URL: https://www.nature.com/articles/s41467-024-54440-6

Title

Development and validation of nomogram models for severe and fatal COVID-19

🤖 Abstract

Background: A major global health crisis caused by a new coronavirus (COVID-19) has led to an increase in infections and deaths. Study aims to develop two predictive models to identify patients at high risk of severe illness or death due to COVID-19. Patients were divided into three groups based on their symptoms. The study used data from 1600 hospitalized patients who developed COVID-19, with one group being the mild category (940), another the severe (433), and a third the fatal (227). Risk factors for severe illness were identified through univariate and direct multiple regression analysis. A final nomogram model was created incorporating the identified risk factors. The model's effectiveness in predicting both severe COVID-19 cases and fatalities was evaluated using ROC curves, calibration tests, and decision curve analysis. Findings: Elevated age, neutrophil (NEU), lactate dehydrogenase (LDH) levels, and decreased lymphocyte (LYM) and albumin (ALB) levels are associated with severe illness in patients. A history of cerebral infarction and cancer were also risk factors for fatalities. Conclusions: The nomogram model identifies high-risk patients based on identified risk factors, which can assist clinicians in timely interventions to reduce the incidence of severe COVID-19 and mortality.

Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) has exhibited escalating contagion and resistance to immunity, resulting in a surge in infections and severe cases. This study endeavors to formulate two nomogram predictive models aimed at discerning patients at heightened risk of severe and fatal outcomes upon hospital admission. The primary objective is to enhance clinical management protocols and mitigate the incidence of severe illness and mortality associated with COVID-19.Methods1600 patients diagnosed with COVID-19 and discharged from Fujian Provincial Hospital were chosen as the subjects of this study. These patients were categorized into three groups: mild group (n= 940), severe group (n= 433), and fatal group (n= 227). The patients were randomly divided into training and validation cohorts in a 7:3 ratio. COVID-19 symptoms were treated as dependent variables, and univariate regression analysis was conducted for the laboratory indicators. Risk factors with p-values greater than 0.05 in the univariate regression analysis were eliminated. The remaining risk factors were then analyzed using direct multiple regression analysis to establish an unadjusted model. Subsequently, risk factors with p-values greater than 0.05 were further removed. Clinical characteristics were added to the model as adjustment factors, and the method of multiple stepwise regression analysis was employed to derive the final fully adjusted model. The severe and fatal COVID-19 models were converted into nomograms, respectively. Receiver operating characteristic (ROC) curves were utilized to evaluate the discrimination of the nomogram models. Calibration was assessed using the Hosmer-Lemeshow test and calibration curves. Clinical benefit was evaluated by decision curve analysis.ResultsCompared to the mild group, individuals in the severe COVID-19 group exhibited significant increases in age, neutrophil (NEU), and lactate dehydrogenase (LDH) levels, alongside notable decreases in lymphocyte (LYM) and albumin (ALB) levels. Nomogram model incorporating age, NEU, LDH, LYM, and ALB demonstrated efficacy in predicting the onset of severe COVID-19 (AUC = 0.771). Furthermore, history of cerebral infarction and cancer, LDH and ALB as risk factors for fatal COVID-19 cases compared to the severe group. The nomogram model comprising these factors was capable of early identification of COVID-19 fatalities (AUC = 0.748).ConclusionsElevated age, NEU, and LDH levels, along with decreased LYM and albumin (ALB) levels, are risk factors for severe illness in hospitalized patients with COVID-19. A history of cerebral infarction and tumors, along with elevated LDH and decreased ALB levels, are risk factors for death in critically ill patients. The nomogram model based on these factors can effectively predict the risk of severe or fatal illness from COVID-19, thereby assisting clinicians in timely interventions to reduce the rates of severe illness and mortality among hospitalized patients. However, the model faces challenges in processing longitudinal data and specific points in time, indicating that there is room for improvement.

Article URL: https://www.nature.com/articles/s41598-024-80310-8

Title

A randomized trial comparing safety, immunogenicity and efficacy of self-amplifying mRNA and adenovirus-vector COVID-19 vaccines

🤖 Abstract

This phase 3 trial compared the safety, tolerability, immunogenicity, and efficacy of two COVID-19 vaccines: ARCT-154 and ChAdOx1-S. Both vaccines were well-tolerated and had similar safety profiles with mild to moderate side effects in adults aged 18-85 years. The vaccine that produced a stronger immune response against COVID-19 also showed higher effectiveness over time, with a greater than 20% reduction in the risk of severe illness.

Abstract

This phase 3 trial compared safety, tolerability, immunogenicity and efficacy of the self-amplifying mRNA COVID-19 vaccine, ARCT-154, with ChAdOx1-S adenovirus-vector vaccine. In four centers in Vietnam adult participants aged 18‒85 years were randomly assigned to receive two doses, 28 days apart, of either ARCT-154 (n = 1186) or ChAdOx1-S (n = 1180). Both vaccines were well tolerated with similar safety and reactogenicity profiles consisting of mainly mild-to-moderate solicited adverse events and few related serious adverse events. Higher neutralizing antibody responses persisting to one-year post-vaccination after ARCT-154 compared with ChAdOx1-S were associated with a generally higher efficacy against COVID-19. In an exploratory analysis relative vaccine efficacy of ARCT-154 vs. ChAdOx1-S against any COVID-19 from Day 36 to Day 394 was 19.8% (95% CI: 4.0–33.0). Self-amplifying mRNA vaccine offers potential immunological advantages in terms of immunogenicity and efficacy over adenovirus-vector vaccine without compromising safety.

Article URL: https://www.nature.com/articles/s41541-024-01017-5

Title

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19

🤖 Abstract

### RNA-dependent RNA polymerase (RdRp) inhibitors present as promising therapeutic targets for COVID-19. ### Researchers develop new antiviral drugs using structure-based drug design approach to inhibit viral proteases, RdRp and 3C-like protease (3CLpro). ### Novel potent non-covalent PLproinhibitors discovered through SBDD, showing improved potency in vitro and in vivo. ### Lead compound GZNL-P36 inhibits SARS-CoV-2 and HCoV-NL63 with EC50 ranging from 58.2 to 306.2 nM and HCoV-229E with EC50 of 81.6 nM and 2.66 μM. ### Oral administration of GZNL-P36 results in improved survival, reduced lung viral loads, and lesions in SARS-CoV-2 mouse model consistent with RNA-seq data analysis. ### The new inhibitors represent a promising approach for treating COVID-19 using RNA-dependent RNA polymerase (RdRp) inhibitors.

Abstract

The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLproinhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLprofrom SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discover a series of novel potent non-covalent PLproinhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLprowith lead compounds reveal that the residues D164 and Q269 around the S2 site are critical for improving the inhibitor’s potency. The lead compound GZNL-P36 not only inhibits SARS-CoV-2 and its variants at the cellular level with EC50ranging from 58.2 nM to 306.2 nM, but also inhibits HCoV-NL63 and HCoV-229E with EC50of 81.6 nM and 2.66 μM, respectively. Oral administration of the GZNL-P36 results in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLproinhibitors represent a promising SARS-CoV-2 therapy.

Article URL: https://www.nature.com/articles/s41467-024-54462-0

Title

Lysosomal “TRAP”: a neotype modality for clearance of viruses and variants

🤖 Abstract

Here is a simplified abstract that a young person can understand: Researchers have created a special "trap" inside cells called lysoTRAP to catch and kill viruses like SARS-CoV-2. They use macrophages (a type of immune cell) as the trap, which helps to clear the virus from the body in a way that is safe and effective. LysoTRAP is able to target and destroy specific parts of the virus that are important for its survival. This "trap" can also catch other types of viruses that have similar targets, making it useful for fighting many different kinds of illness.

Abstract

The binding of viruses to host-entry factor receptors is an essential step for viral infection. Many studies have shown that macrophages can internalize viruses and degrade them in lysosomes for clearance in vivo. Inspired by these natural behaviors and using SARS-CoV-2 as a testbed, we harvest lysosomes from activated macrophages and anchor the protein-receptor ACE2 as bait, thus constructing a lysosomal “TRAP” (lysoTRAP) that selectively captures, internalizes, and eventually degrades SARS-CoV-2. Through experiments with cells, female mice, female hamsters, and human lung organoids, we demonstrate that lysoTRAP effectively clears SARS-CoV-2. Importantly, unlike therapeutic agents targeting SARS-CoV-2 spike protein, lysoTRAP remains effective against nine pseudotyped variants and the authentic Omicron variant, demonstrating its resistance to SARS-CoV-2 mutations. In addition to the protein-receptor ACE2, we also extend lysoTRAP with the saccharide-receptor sialic acid and verify its excellent antiviral effect against H1N1, highlighting the flexibility of our “TRAP” platform in fighting against various viruses.

Article URL: https://www.nature.com/articles/s41467-024-54505-6

Title

Outcome of SARS-CoV-2 reinfection depends on genetic background in female mice

🤖 Abstract

Here is a simplified abstract: A new strain of COVID-19 (B.1.351) can make people who have been vaccinated or exposed to it more likely to get infected again. This happens because their immune system doesn't respond well to the specific virus and starts producing antibodies that can prevent them from fighting it off. The severity of COVID-19 also depends on how strong a person's immune system is, which varies depending on genetic factors. In one study, researchers examined how different groups of mice (with genetic backgrounds) responded to infection with different strains of the virus. They found that some types of strain can trigger severe disease in people who are vaccinated or exposed, while others may protect against it. The study also looked at what happens inside the body after a person is infected with this new strain and how their immune system responds. It found that certain cells in the lungs (in the air sacs) respond differently to infection by different groups of mice, which could explain why some people get more severe disease while others don't. Overall, the study suggests that COVID-19 severity depends on a combination of factors, including how strong the immune system is and how the body responds to the virus.

Abstract

Antigenically distinct SARS-CoV-2 variants increase the reinfection risk for vaccinated and previously exposed population due to antibody neutralization escape. COVID-19 severity depends on many variables, including host immune responses, which differ depending on genetic predisposition. To address this, we perform immune profiling of female mice with different genetic backgrounds –transgenic K18-hACE2 and wild-type 129S1– infected with the severe B.1.351, 30 days after exposure to the milder BA.1 or severe H1N1. Prior BA.1 infection protects against B.1.351-induced morbidity in K18-hACE2 but aggravates disease in 129S1. H1N1 protects against B.1.351-induced morbidity only in 129S1. Enhanced severity in B.1.351 re-infected 129S1 is characterized by an increase of IL-10, IL-1β, IL-18 and IFN-γ, while in K18-hACE2 the cytokine profile resembles naïve mice undergoing their first viral infection. Enhanced pathology during 129S1 reinfection cannot be attributed to weaker adaptive immune responses to BA.1. Infection with BA.1 causes long-term differential remodeling and transcriptional changes in the bronchioalveolar CD11c+ compartment. K18-hACE2 CD11c+ cells show a strong antiviral defense expression profile whereas 129S1 CD11c+ cells present a more pro-inflammatory response upon restimulation. In conclusion, BA.1 induces cross-reactive adaptive immune responses in K18-hACE2 and 129S1, but reinfection outcome correlates with differential CD11c+ cells responses in the alveolar space.

Article URL: https://www.nature.com/articles/s41467-024-54334-7

Title

Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections

🤖 Abstract

Research study compares immune system response to different types of viral infections. It finds that the body's reaction to a virus can be affected by the type and severity of the infection, as well as how long it lasts. The study looks at how soluble inflammatory mediators (small molecules involved in inflammation) change over time in patients with hepatitis C or SARS-CoV-2 after treatment or resolution of their infections.

Abstract

Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3–9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection.

Article URL: https://www.nature.com/articles/s41598-024-79909-8

Title

The value of environmental surveillance for pandemic response

🤖 Abstract

Environmental sampling surveillance (ESS) technologies are being used more widely during pandemics to gather valuable data on disease outbreaks. However, not all areas have access to these systems, which means public health officials need guidance on when and if to use them. A new study aims to create a model that can help make decisions about ESS use based on factors such as the type of pathogen causing an outbreak and how often it occurs in other parts of the world. Using a real-life example from the COVID-19 pandemic, researchers found that an ESS system could potentially save thousands of lives by providing early warnings for disease outbreaks. Their research suggests that using ESS systems effectively depends on factors such as how deadly the pathogen is and whether or not effective public health interventions are in place. Even if pathogens like SARS-Cov-2 emerge rarely, their study shows that ESS systems can still provide valuable information and potentially save lives over time. The researchers also found that the value of an ESS system increases for more contagious and deadly pathogens but depends on the effectiveness of local public health efforts. As a result, their findings could help policymakers decide when to invest in ESS systems and how to scale them up over time.

Abstract

Environmental sampling surveillance (ESS) technologies, such as wastewater genomic surveillance and air sensors, have been increasingly adopted during the COVID-19 pandemic to provide valuable information for public health response. However, ESS coverage is not universal, and public health decision-makers need support to choose whether and how to expand and sustain ESS efforts. This paper introduces a model and approach to quantify the value of ESS systems that provide leading epidemiological indicators for pandemic response. Using the COVID-19 pandemic as a base-case scenario, we quantify the value of ESS systems in the first year of a new pandemic and demonstrate how the value of ESS systems depends on biological and societal parameters. Under baseline assumptions, an ESS system that provides a 5-day early warning relative to syndromic surveillance could reduce deaths from 149 (95% prediction interval: 136–169) to 134 (124–144) per 100,000 population during the first year of a new COVID-19-like pandemic, resulting in a net monetary benefit of $1,450 ($609-$2,740) per person. The system’s value is higher for more transmissible and deadly pathogens but hinges on the effectiveness of public health interventions. Our findings also suggest that ESS systems would provide net-positive benefits even if they were permanently maintained and pathogens like SARS-Cov-2 emerged once every century or less frequently. Our results can be used to prioritize pathogens for ESS, decide whether and how to expand systems to currently uncovered populations, and determine how to scale surveillance systems’ coverage over time.

Article URL: https://www.nature.com/articles/s41598-024-79952-5

Title

Morbidity of SARS-CoV-2 in the evolution to endemicity and in comparison with influenza

🤖 Abstract

BackgroundThere are three possible ways the COVID-19 pandemic might change: ongoing severity, influenza-like severity, and becoming less severe over time. MethodsWe analyzed data from the US National Covid Cohort Collaborative, CDC COVID-NET, and CDC Fluview to see how the pandemic might evolve under each scenario. We also looked at the response of people with SARS-CoV-2 infections to treatment and hospitalization rates in wastewater samples. ResultsThe analysis shows that: * People with SARS-CoV-2 infections tend to have similar symptoms as those with influenza. * However, when looking at how many people are hospitalized for SARS-CoV-2, the pandemic is actually much less severe than it was for influenza. * The treatments used to fight SARS-CoV-2 work well. ConclusionsAs the pandemic transitions from being an outbreak to a more manageable situation, its symptoms will continue to decline.

Abstract

BackgroundThere are three possible SARS-CoV-2 post-pandemic scenarios: (i) ongoing severity, (ii) influenza-like severity, and (iii) a transition to an endemic disease with lesser morbidity similar to that of other human coronaviruses.MethodsTo assess a possible evolution of the pandemic under the three scenarios, we use data from the US National Covid Cohort Collaborative, CDC COVID-NET, and CDC Fluview and from the WastewaterSCAN Dashboard. We include influenza disease and treatment response as benchmark. The US National Covid Cohort Collaborative allows the quantification of viral-specific morbidity using electronic health records from 424,165 SARS-CoV-2 cases, 53,846 influenza cases, and 199,971 uninfected control subjects from 2021–2022. Evolution of hospitalization rates is estimated from the correlation between national SARS-CoV-2 and influenza hospitalization data and viral gene copies in wastewater.ResultsOur findings reveal that medically attended SARS-CoV-2 infections exhibit similar morbidity to influenza [indicative of scenario (ii)], but SARS-CoV-2 hospitalization rates are one order of magnitude lower than influenza when considering virus concentration in wastewater [indicative of scenario (iii)]. Moreover, SARS-CoV-2 displays a more favorable response to antiviral therapy.ConclusionsOur analysis confirms a rapid decline in SARS-CoV-2 morbidity as it transitions to an endemic state.

Article URL: https://www.nature.com/articles/s43856-024-00633-5

Title

Reduced cross-protective potential of Omicron compared to ancestral SARS-CoV-2 spike vaccines against potentially zoonotic coronaviruses

🤖 Abstract

Here is the simplified abstract: A global campaign to vaccinate people against COVID-19 has helped build immunity against other coronavirus viruses with potential to jump from animals to humans. Researchers tested this by giving mice models of COVID-19 and then checking for antibodies that can fight multiple human strains, including ACE2-binding ones. The results showed that the vaccines based on Omicron spike sequences were much less effective at protecting against these other viruses compared to previous vaccines like SARS-CoV-2.

Abstract

The COVID-19 pandemic has emphasised the importance of vaccines and preparedness against viral threats crossing species barriers. In response, a worldwide vaccination campaign targeting SARS-CoV-2 was implemented, which provides some cross-protective immunological memory to other coronavirus species with zoonotic potential. Following a vaccination regimen against SARS-CoV-2 spike in a preclinical mouse model, we were able to demonstrate the induction of neutralizing antibodies towards multiple human ACE2 (hACE2)-bindingSarbecovirusspikes. Importantly, compared to vaccines based on the SARS-CoV-2 Reference strain, vaccines based on Omicron spike sequences induced drastically less broadly cross-protective neutralizing antibodies against other hACE2-binding sarbecoviruses. This observation remained true whether the vaccination regimens were based on protein subunit or mRNA / LNP vaccines. Overall, while it may be necessary to update vaccine antigens to combat the evolving SARS-CoV-2 virus for enhanced protection from COVID-19, Reference-based vaccines may be a more valuable tool to protect against novel coronavirus zoonoses.

Article URL: https://www.nature.com/articles/s44298-024-00067-9

Title

Sensitivity of rodents to SARS-CoV-2: Gerbils are susceptible to SARS-CoV-2, but guinea pigs are not

🤖 Abstract

### Study Helps Predict Risk of SARS-CoV-2 Transmission from Humans to Pets Scientists studied how well different rodents (guinea pigs and gerbils) can contract a virus called SARS-CoV-2 from people. They found that: * Gerbils are highly susceptible to the virus * Guinea pigs are not as sensitive

Abstract

Syrian hamster are sensitive to SARS-CoV-2 and widely used as an animal model of COVID-19. In contrast, mice are not readily infected by the ancestral strains of SARS-CoV-2 because of differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Thus, even among rodents, susceptibility to SARS-CoV-2 varies. Knowledge of virus transmissibility from humans to pet rodents is important for public health to assess the potential for transmission in the home and pet breeding and selling facilities. In this study, we assessed the sensitivity of guinea pigs and gerbils to SARS-CoV-2 isolated from humans, and found that gerbils are susceptible to SARS-CoV-2, but guinea pigs are not. Pet sellers often display hamsters with high susceptibility to SARS-CoV-2 in the same area as gerbils, so caution should be exercised during COVID-19 outbreaks.

Article URL: https://www.nature.com/articles/s44298-024-00068-8

Title

Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population

🤖 Abstract

Postmortem analysis of single cells has greatly improved our understanding of respiratory diseases such as COVID-19. However, there is limited research on how these diseases affect people from different regions, including Africa, where HIV, malaria, and environmental exposures may play a significant role in disease pathobiology and treatment outcomes. This study aimed to understand the lung disease associated with COVID-19 in Malawian adults. Researchers analyzed the cells found in lungs, blood, and nasal tissue of 9 people who had died from COVID-19 and 7 people who did not have the virus. The results showed that the lung damage caused by COVID-19 is similar across different populations, but there are differences in how it affects each group. The study also looked at the immune responses in the blood and lungs of these individuals, finding that some people had a stronger response to certain proteins in their blood. Specifically, people with HIV did not have as strong an immune response. Overall, this research provides valuable information about the cellular mechanisms underlying COVID-19 lung disease and highlights the importance of studying how different diseases affect people from diverse backgrounds.

Abstract

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n= 9) and without (n= 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages. HIV status had minimal impact on histology or immunopathology. Our study provides a data resource and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.

Article URL: https://www.nature.com/articles/s41591-024-03354-3

Title

Bias and negative values of COVID-19 vaccine effectiveness estimates from a test-negative design without controlling for prior SARS-CoV-2 infection

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Scientists have been studying how well vaccines work to protect against certain diseases. However, it can be difficult to tell if someone has had an infection before they were vaccinated. To figure this out, researchers created "test-negative designs" that helped them make more accurate estimates of vaccine effectiveness. They looked at data from a COVID-19 outbreak and found that when people who were vaccinated had fewer protection against the disease than those who weren't, it could lead to incorrect conclusions about how safe vaccines are. This happened because they didn't take into account whether these vaccinated individuals actually got infected with the disease in the first place. The researchers also found that test-negative designs, which were used immediately after a new vaccine was rolled out, introduced more bias than traditional methods and potentially led to incorrect interpretations of vaccine effectiveness.

Abstract

Test-negative designs (TNDs) are used to assess vaccine effectiveness (VE). Protection from infection-induced immunity may confound the association between case and vaccination status, but collecting reliable infection history can be challenging. If vaccinated individuals have less infection-induced protection than unvaccinated individuals, failure to account for infection history could underestimate VE, though the bias is not well understood. We simulated individual-level SARS-CoV-2 infection and COVID-19 vaccination histories and a TND. VE against symptomatic infection and VE against severe disease estimates unadjusted for infection history underestimated VE compared to estimates adjusted for infection history, and unadjusted estimates were more likely to be below 0%, which could lead to an incorrect interpretation that COVID-19 vaccines are harmful. TNDs assessing VE immediately following vaccine rollout introduced the largest bias and potential for negative VE against symptomatic infection. Despite the potential for bias, VE estimates from TNDs without prior infection information are useful because underestimation is rarely more than 8 percentage points.

Article URL: https://www.nature.com/articles/s41467-024-54404-w

Title

Intranasal delivery of a subunit protein vaccine provides protective immunity against JN.1 and XBB-lineage variants

🤖 Abstract

The mucosal immune system plays a crucial role in preventing respiratory infections, but recent cases of SARS-CoV-2 have raised concerns about their ability to fight off infections. Researchers developed an intranasal COVID-19 vaccine that could help prevent these infections and protect against future outbreaks. This vaccine works by stimulating the body's immune system to produce antibodies that can recognize and attack the virus, providing long-lasting protection. The study also found that this type of vaccine is more effective as a booster shot than others and can provide additional protection against viral infections in real-life situations.

Abstract

The mucosal immune response plays a crucial role in the prevention of respiratory viruses. Given the risk of recurrent SARS-CoV-2 infections in the population, the rapid development of next-generation intranasal COVID-19 vaccines with high safety and efficacy is paramount. In the current study, we developed a protein-based intranasal vaccine comprising the XBB.1.5 receptor binding domain (RBD)-derived trimeric recombinant protein (RBDXBB.1.5-HR) and an MF59-like oil-in-water adjuvant. Intranasal administration of RBDXBB.1.5-HR vaccine elicited robust and sustained humoral immune responses in mice and rats, resulting in high levels of neutralizing antibodies against XBB-lineage subvariants, with protection lasting for at least six months. The intranasal RBDXBB.1.5-HR vaccine generated potent mucosal immune responses, characterized by the inductions of tissue-resident T (TRM) cells, local cellular immunity, germinal center, and memory B cell responses in the respiratory tract. The combination of intramuscular and intranasal delivery of the RBDXBB.1.5-HR vaccine demonstrated exceptional systemic and mucosal protective immunity. Furthermore, intranasal delivery of RBDXBB.1.5-HR vaccine as a heterologous booster shot showed more effective boosting effects after mRNA administration compared to homologous vaccination, as evidenced by the induction of superior systemic and extra mucosal immune response. Importantly, the intranasal RBDXBB.1.5-HR vaccine conferred efficient protection against the challenge with authentic EG.5.1 viruses in vivo. These findings identify the intranasal RBDXBB.1.5-HR vaccine as a potential mucosal vaccine candidate for the prevention of SARS-CoV-2 infection.

Article URL: https://www.nature.com/articles/s41392-024-02025-6

Title

Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine

🤖 Abstract

As COVID-19 continues to evolve, a new vaccine is needed to protect against the most contagious variants. Researchers have developed a vaccine that contains changes specific to the Omicron XBB.1.5 variant and has shown improved protection against this strain compared to previous vaccines. The vaccine also induces strong immune responses, including Th1 CD4+ and IFNγ+ T cells.

Abstract

As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative to the original BNT162b2 backbone, in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation and adopts a flexible, predominantly open, state, with high affinity for the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose series in naive mice. Strong S-specific Th1 CD4+and IFNγ+CD8+T cell responses were also observed. These findings, together with real world performance of the XBB.1.5-adapted vaccine, suggest that preclinical data for the monovalent Omicron XBB.1.5-adapted BNT162b2 was predictive of protective immunity against dominant SARS-CoV-2 strains.

Article URL: https://www.nature.com/articles/s41541-024-01013-9

Title

Characterizing the interactions between influenza and respiratory syncytial viruses and their implications for epidemic control

🤖 Abstract

Here's a simplified version of the abstract: Pathogens, like viruses and bacteria, can interact with each other in complex ways that affect how people get infected and recover from diseases. Researchers have discovered that certain infections, such as the flu and RSV, have a strong and lasting impact on each other when they occur together. By using advanced mathematical modeling techniques and data from two different countries, scientists found this interaction is significant enough to be studied in detail. They also explored how live vaccines against one of these diseases could reduce the risk of getting infected with the other. The study's findings suggest that understanding these interactions can help predict which vaccines may have a greater impact on public health.

Abstract

Pathogen-pathogen interactions represent a critical but little-understood feature of infectious disease dynamics. In particular, experimental evidence suggests that influenza virus and respiratory syncytial virus (RSV) compete with each other, such that infection with one confers temporary protection against the other. However, such interactions are challenging to study using common epidemiologic methods. Here, we use a mathematical modeling approach, in conjunction with detailed surveillance data from Hong Kong and Canada, to infer the strength and duration of the interaction between influenza and RSV. Based on our estimates, we further utilize our model to evaluate the potential conflicting effects of live attenuated influenza vaccines (LAIV) on RSV burden. We find evidence of a moderate to strong, negative, bidirectional interaction, such that infection with either virus yields 40-100% protection against infection with the other for one to five months. Assuming that LAIV reduces RSV susceptibility in a similar manner, we predict that the impact of such a vaccine at the population level would likely depend greatly on underlying viral circulation patterns. More broadly, we highlight the utility of mathematical models as a tool to characterize pathogen-pathogen interactions.

Article URL: https://www.nature.com/articles/s41467-024-53872-4

Title

Boosting neuraminidase immunity in the presence of hemagglutinin with the next generation of influenza vaccines

🤖 Abstract

### Abstract ### Neuraminidase (NA) plays a key role in viral replication, making it crucial for the spread of flu viruses. Despite some evidence suggesting that people with antibodies against NA may be less susceptible to illness, current flu vaccines focus primarily on one protein called hemagglutinin (HA). Researchers have discovered that using a different protein called neuraminidase (NA) can stimulate strong immune responses in mice and ferrets. By adding NA to flu vaccines, these animals developed mild flu symptoms when exposed to a new strain of the virus, but also showed reduced severity of the illness. The results suggest that incorporating NA into flu vaccines could increase their effectiveness by boosting immunity against NA.

Abstract

Neuraminidase (NA), the second most abundant surface glycoprotein on the influenza virus, plays a key role in viral replication and propagation. Despite growing evidence showing that NA-specific antibodies correlate with resistance to disease in humans, current licensed vaccines focus almost entirely on the hemagglutinin (HA) antigen. Here, we demonstrate that recombinant NA (rNA) protein is highly immunogenic in both naïve mice and ferrets, as well as in pre-immune ferrets, irrespective of the level of match with preexisting immunity. Ferrets vaccinated with rNA developed mild influenza disease symptoms upon challenge with human H3N2 influenza virus, and anti-NA antibody responses appeared correlated with reduction in disease severity. The addition of rNA to a quadrivalent HA-based vaccine induced robust NA-specific humoral immunity in ferrets, while retaining the ability to induce HA-specific immunity. These results demonstrate that the addition of rNA is a viable option to increase immunogenicity and potentially efficacy versus currently licensed influenza vaccines by means of boosting NA immunity.

Article URL: https://www.nature.com/articles/s41541-024-01011-x

Title

Altered leukocyte pattern and inflammatory markers in unvaccinated long covid patients: a cross-sectional study

🤖 Abstract

Research by scientists found that people who have COVID-19 for more than three months tend to have different levels of certain immune cells and chemicals in their blood compared to those with milder symptoms or shorter illnesses. The study focused on individuals living in the Amazon region, where such research is scarce. It analyzed blood samples from patients to see how they changed over time. The findings suggest that people with Long Covid may have persistent inflammation in their bodies, which can last for a year or more after their illness ends.

Abstract

Long Covid results from the damage caused by SARS-CoV-2, involving the release of cytokines and the continuous activation of immune cells. This cross-sectional study investigates leukocyte and cytokine profiles in Long Covid patients in the Amazon, a region where such studies are limited. Blood samples were analysed for differential leukocyte counts and cytokine levels. We suggest elevated lymphocyte counts in hospitalised patients and those with severe COVID-19. Higher eosinophil counts were observed in patients with up to three months of Long Covid, and increased monocyte counts in those with up to six months. IL-2 levels were higher in patients with fewer symptoms and Long Covid duration of more than three months, whereas IL-10 may remain elevated for up to 12 months. We suggest positive correlations between neutrophils, monocytes, eosinophils, and lymphocytes with different cytokines (IFN-γ, IL-6, IL-4, IL-17a, IL-2). Women were associated with lower hospitalisation rates and longer durations of Long Covid; increased lymphocyte counts were linked to hospitalisation due to COVID-19, while higher monocyte counts were associated with Long Covid durations of up to six months. We suggest that Long Covid patients may exhibit alterations in inflammatory markers, indicating a persistently pro-inflammatory microenvironment that tends to diminish after 12 months of Long Covid.

Article URL: https://www.nature.com/articles/s41598-024-75920-1

Title

Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform

🤖 Abstract

A type of bile acid called ursodeoxycholic acid (UDCA) has been shown to be effective in preventing serious complications from COVID-19 in people with liver disease. A large study found that taking UDCA lowered the risk of hospitalization or death due to COVID-19, and suggests it may also reduce this risk in others at high risk of severe illness.

Abstract

BackgroundBiological evidence suggests ursodeoxycholic acid (UDCA)—a common treatment of cholestatic liver disease—may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).MethodsWith the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders.ResultsWe identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67–0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%–1.69%).ConclusionsWe found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

Article URL: https://www.nature.com/articles/s43856-024-00664-y

Title

Obesity does not influence SARS-CoV-2 humoral vaccine immunogenicity

🤖 Abstract

Here's a simplified version of the abstract: Obesity affects how well the body responds to vaccines against diseases like COVID-19, including antibodies and immune cells that fight off infections. Research from over 34 months in 697 people, mostly women with no obesity, found that there was no consistent difference in how well they responded to SARS-CoV-2 vaccine. The study controlled for other factors and didn't find a significant effect of obesity on peak levels or types of antibodies produced by the immune system.

Abstract

Obesity is a recognized factor influencing immune function and infectious disease outcomes. Characterization of the influence of obesity on SARS-CoV-2 humoral vaccine immunogenicity is required to properly tailor vaccine type (mRNA, viral-vector, protein subunit vaccines) and dosing schedule. Data from a prospective cohort study collected over 34 months was used to evaluate the slope of antibody production and decay and neutralizing capacity following SARS-CoV-2 vaccination in individuals with and without obesity at baseline. Most participants were female (65.4%), white (92.4%), and received mRNA vaccines. 210 were obese and 697 non-obese. Sex and infection-acquired immunity were identified as effect modifiers for the relationship between obesity and COVID-19 vaccine humoral immunogenicity. No consistent influence of obesity on peak titres, titre retention, antibody isotype (IgG, IgM, IgA), or neutralization was identified when controlling for other key variables. It may not be necessary to consider this variable when developing SARS-CoV-2 vaccine dosing strategies.

Article URL: https://www.nature.com/articles/s41541-024-01022-8

Title

Predictive risk models for COVID-19 patients using the multi-thresholding meta-algorithm

🤖 Abstract

A machine learning model has been developed to predict complications leading to ICU admission or death among COVID-19 patients in hospitals. The goal is to identify minority classes of discharged patients who are at high risk. To address dataset imbalance, a new methodology called Multi-Thresholding meta-algorithm (MTh) is introduced. This method adjusts class probabilities using misclassification costs and is effective in imbalanced datasets. Bayesian networks are used to create a robust predictive model. The model finds that certain patient characteristics, such as high Charlson Index and pre-existing conditions, significantly influence the risk of ICU admission and mortality. An explanatory model also shows how these factors interact with therapeutic limits to assess overall risk.

Abstract

This study aims to develop a Machine Learning model to assess the risks faced by COVID-19 patients in a hospital setting, focusing specifically on predicting the complications leading to Intensive Care Unit (ICU) admission or mortality, which are minority classes compared to the majority class of discharged patients. We operate within a multiclass framework comprising three distinct classes, and address the challenge of dataset imbalance, a common source of model bias. To effectively manage this, we introduce the Multi-Thresholding meta-algorithm (MTh), an innovative output-level methodology that extends traditional thresholding from binary to multiclass classification. This methodology dynamically adjusts class probabilities using misclassification costs, making it highly effective in imbalanced datasets. Our approach is further enhanced by integrating the simplicity, transparency, and effectiveness of Bayesian networks to create a robust predictive model. Using patient admission data, the model accurately identifies key risk and protective factors for COVID-19 outcomes. Our findings indicate that certain patient characteristics, such as high Charlson Index and pre-existing conditions, significantly influence the risk of ICU admission and mortality. Moreover, we introduce an explanatory model that elucidates the interrelationships among these factors, demonstrating the influence of therapeutic limits on the overall risk assessment of COVID-19 patients. Overall, our research provides a significant contribution to the field of Machine Learning by offering a novel solution for multiclass classification in the context of imbalanced datasets. This model not only enhances predictive accuracy but also supports critical decision-making processes in healthcare, potentially improving patient outcomes and optimizing clinical resource allocation.

Article URL: https://www.nature.com/articles/s41598-024-77386-7

Title

Preclinical evaluation of a universal inactivated influenza B vaccine based on the mosaic hemagglutinin-approach

🤖 Abstract

A new flu vaccination approach has been developed, using antibodies (mHA) from exotic avian viruses that are similar to those causing human diseases but more mild and less likely to be contagious. This new method stimulates a strong immune response by targeting specific areas on the influenza B virus that humans have evolved to be resistant to. Combining these mHA vaccines with adjuvants like Toll-like receptor-9 agonists and oils increases their effectiveness.

Abstract

We have developed a new universal influenza B vaccination strategy based on inactivated influenza B viruses displaying mosaic hemagglutinins (mHAs). Recombinant mHA viruses were constructed by replacing the four major antigenic sites of influenza B virus HAs, with those from exotic avian influenza A virus HAs. Sequential vaccination of naïve mice with mHA-based vaccines elicited higher immune responses towards the immuno-subdominant conserved epitopes of the HA than vaccination with wildtype viruses. Among the different preparations tested, mHA split vaccines were less immunogenic than their whole inactivated virus counterparts. This lower immunogenicity was overcome by the combination with adjuvants. mHA split vaccines adjuvanted with a Toll-like receptor-9 agonist (CpG 1018) increased Th1 immunity and invivocross-protection, whereas adjuvanting with an MF59-like oil-in-water nano-emulsion (AddaVax) enhanced and broadened humoral immune responses and antibody-mediated cross-protection. The mHA vaccines with or without adjuvant were subsequently evaluated in mice that were previously immunized to closely mimic human pre-existing immunity to influenza B viruses and the contribution of innate and cellular immunity was evaluated in this model. We believe these preclinical studies using the mHA strategy represent a major step toward the evaluation of a universal influenza B virus vaccine in clinical trials.

Article URL: https://www.nature.com/articles/s41541-024-01014-8

Title

High throughput screen identifies lysosomal acid phosphatase 2 (ACP2) to regulate IFN-1 responses to potentiate oncolytic VSV∆51 activity

🤖 Abstract

Strategies to improve oncolytic virotherapy (OV) by enhancing innate immunity are being researched. A new approach involves using vanadium-based compounds as inhibitors of pan-phosphatase proteins (PPs), which can potentiate OV treatment. To boost effectiveness, a high-throughput screen was conducted using silencing RNA targeting human PPs to identify compounds that enhance VSV∆51 infectivity and oncolysis. One key protein, lysosomal acid phosphatase 2 (ACP2), was found to be particularly effective in increasing VSV∆51 viral titers. Knocking down ACP2 significantly increased the virus's growth. Analysis of RNA sequencing revealed that ACP2 regulates antiviral type I interferon signaling pathways similar to vanadium. To further enhance OV treatment, a short-hairpin RNA (shRNA) against ACP2 was designed and introduced into VSV∆51 under a miR-30 promoter. This engineered virus produced the miR-30 promoter, knocked down ACP2, and ultimately increased viral production compared to its non-targeting counterpart. This study suggests that targeting proteins like ACP2 may improve oncolytic virotherapy by boosting the body's innate immunity against cancer cells, thereby increasing treatment efficacy.

Abstract

Strategies in genetic and pharmacological modulation of innate immunity to enhance oncolytic virotherapy (OV) efficacy are being explored. We have recently characterized the ability for vanadium-based compounds, a class of pan-phosphatase (PP) inhibitors, to potentiate OVs. We next sought to identify PPs that could be targeted to enhance OVs, akin to vanadium. By conducting a high-throughput screen of a library of silencing RNA (siRNA) targeting human PPs, we uncovered several PPs that robustly enhanced infectivity and oncolysis of the oncolytic vesicular stomatitis virus (VSV∆51). Knockdown of our top validated hit, lysosomal acid phosphatase 2 (ACP2), increased VSV∆51 viral titers by over 20-fold. In silico analysis by RNA sequencing revealed ACP2 to regulate antiviral type I interferon (IFN-1) signaling pathways, similar to vanadium. To further exploit this mechanism for therapeutic gain, we encoded a short-hairpin RNA (shRNA) against ACP2 into oncolytic vesicular stomatitis virus (VSV∆51) under a miR-30 promoter. This bioengineered OV demonstrated expression of the miR-30 promoter, knockdown of ACP2, repression and ultimately, showed markedly enhanced viral VSV∆51 particle production compared to its non-targeting control counterpart. Altogether, this study identifies IFN-1 regulating PP targets, namely ACP2, that may prove instrumental in increasing the therapeutic efficacy of OVs.

Article URL: https://www.nature.com/articles/s41598-024-76855-3

Title

Microfluidic qPCR for detection of 21 common respiratory viruses in children with influenza-like illness

🤖 Abstract

Multiple viral infections lead to high illness and death rates worldwide. However, current surveillance platforms focus mainly on seasonal influenza viruses. The COVID-19 pandemic highlights the importance of a more comprehensive approach, using advanced technologies like microfluidic quantitative polymerase chain reaction (qPCR) for detecting multiple respiratory viruses in children presenting with flu-like symptoms. This study analyzed samples from children aged 24 to 59 months diagnosed with influenza-like illness in The Gambia and found that common viral infections include rhinovirus and adenovirus, as well as other viruses like parainfluenza virus 3, influenza B, and human metapneumovirus B. A significant proportion of positive samples had multiple viruses detected. These findings suggest that microfluidic qPCR can be a useful tool for comprehensive detection of multiple respiratory viruses in surveillance platforms.

Abstract

Multiple respiratory viruses lead to high morbidity and mortality, yet global surveillance platforms focus primarily on seasonal influenza viruses. The COVID-19 pandemic and new RSV vaccines highlight the importance of a broader approach. Upper respiratory tract swabs from children aged 24–59 months presenting with influenza-like illness in The Gambia were collected during follow-up of a live-attenuated influenza vaccine randomised controlled trial in 2017–18. A microfluidic quantitative polymerase chain reaction (qPCR) assay was established and used to detect 21 respiratory viruses. 76.6% of samples had one or more viruses detected (n = 121/158). The viruses detected most frequently were rhinovirus (n = 37/158, 23.4%) and adenovirus (n = 34/158, 21.5%), followed by parainfluenza virus 3, influenza B and human metapneumovirus B. A third of positive samples had multiple viruses detected (two n = 31/121, 25.6%; three n = 9/121, 7.4%). Our data demonstrates how microfluidic qPCR is a useful tool for high-throughput, comprehensive detection of multiple respiratory viruses in surveillance platforms. Rapidly changing epidemiology exemplifies the need for new, broader approaches to virus surveillance in low-resource settings to respond to future epidemics and to guide the need for and use of new prevention and therapeutic measures.

Article URL: https://www.nature.com/articles/s41598-024-79407-x

Title

Interference of small compounds and Mg2+with dsRNA-binding fluorophores compromises the identification of SARS-CoV-2 RdRp inhibitors

🤖 Abstract

Here's a simplified version of the abstract: Researchers studied compounds suspected to be viral RNA-dependent RNA polymerases inhibitors (RdRp inhibitors) to develop effective treatments for COVID-19. They tested these compounds in biochemical assays using different methods, but found that most small molecules interfere with a test method that measures enzyme activity. As a result, they concluded that this testing method was unreliable and needed independent validation. They also discovered that one of the potential RdRp inhibitors tested is actually an inhibitor of multiple enzymes, which means it's not specific to SARS-CoV-2's RNA polymerase.

Abstract

The COVID-19 pandemic highlighted the need for the rapid development of antiviral therapies. Viral RNA-dependent RNA polymerases (RdRp) are promising targets, and numerous virtual screenings for potential inhibitors were conducted without validation of the identified hits. Here we have tested a set of presumed RdRp inhibitors in biochemical assays based on fluorometric detection of RdRp activity or on the electrophoretic separation or RdRp products. We find that fluorometric detection of RdRp activity is unreliable as a screening method because many small compounds interfere with fluorophore binding to dsRNA, and this effect is enhanced by the Mg2+metal ions used by nucleic acid polymerases. The fact that fluorimetric detection of RdRp activity leads to false-positive hits underscores the requirement for independent validation methods. We also show that suramin, one of the proposed RdRp inhibitors that could be validated biochemically, is a multi-polymerase inhibitor. While this does not hinder its potential as an antiviral agent, it cannot be considered an specific inhibitor of SARS-CoV-2 RdRp.

Article URL: https://www.nature.com/articles/s41598-024-78354-x

Title

A cross-sectional study of fundus lesion characteristics in patients with acute visual impairment caused by COVID-19 infection

🤖 Abstract

A study investigated the characteristics of visual dysfunction and fundus lesions in patients with COVID-19 pneumonia. The study looked at 48 patients who were infected with COVID-19 between December 2022 and February 2023. It found that most patients had bilateral involvement and showed abnormal retinal changes on various tests, including OCT, MCI, and IR.

Abstract

To investigate the characteristics of acute visual dysfunction and fundus lesions in patients with COVID-19 pneumonia. A retrospective case series study was conducted. Data from 48 patients (96 eyes) with COVID-19 infection who presented to our ophthalmology department with acute onset visual disturbance between December 5, 2022, and February 28, 2023 were collected. Asymptomatic patients and those who had already recovered were excluded. Data collected included patient demographics, ophthalmic examinations, multicolor imaging (MCI), infrared autofluorescence (IR), spectral-domain optical coherence tomography (OCT), fundus fluorescein angiography (FFA). Of the 48 patients, 15 were male and 33 were female, with a mean age of 32 years. All patients had bilateral involvement. OCT showed hyperreflective signals in the outer plexiform layer and outer nuclear layer of the macular region in all 96 eyes of 48 patients (100%). Additionally, 66 eyes of 33 patients (68.8%) of eyes demonstrated abnormal reflectivity in the ellipsoid and interdigitation zones. MCI revealed petaloid or wedge-shaped hyperreflective areas in the macula in 46 (47.9%) of eyes, corresponding to hyporeflective areas on IR. Cotton-wool spots were observed in the peripapillary or posterior pole area in 54 (56.3%) of eyes. COVID-19 infection can lead to acute, bilateral, symmetric, and widespread retinal damage. Characteristic findings can be observed in ophthalmological examinations such as OCT, MCI, and IR.

Article URL: https://www.nature.com/articles/s41598-024-79509-6

Title

Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants

🤖 Abstract

A new vaccine is being developed that targets a specific protein on the surface of the SARS-CoV-2 virus, which has led to multiple variants of the disease. To combat this, researchers are working on developing a treatment that can neutralize the virus even when it mutates and becomes harder to target. This vaccine uses a human antibody that was made by someone who had recovered from COVID-19 and is specifically designed to bind to the protein of SARS-CoV-2.

Abstract

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a differential staining strategy with a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) – ACE2 fusion protein and a native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan-1, the more recent Omicron JN.1 strain, and SARS-CoV. 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain. Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

Article URL: https://www.nature.com/articles/s44298-024-00063-z

Title

Sex differences in pneumonia risk during COVID-19 in Mexico

🤖 Abstract

This study aimed to assess the risk of pneumonia among adults with COVID-19, particularly based on their sex, during two phases of the pandemic in Mexico. A large dataset was analyzed from 2020 to 2023. The results showed that men had a higher risk of severe manifestations of the disease compared to women.

Abstract

This study aimed to evaluate the pneumonia risk based on the patient’s sex during the COVID-19 pandemic and the early months of the endemic phase of the disease in Mexico. A retrospective cohort study was conducted using a dataset resulting from the epidemiological surveillance of COVID-19 (February 2020 to August 2023). Data from 1.6 million adults with laboratory-positive disease, were analyzed. Risk ratios (RR) and 95% confidence intervals (CI), computed through generalized linear regression models, were used. The overall risk of pneumonia was 9.3% (95% CI 9.2–9.4%), with sex-specific estimates of 7.0% (95% CI 6.9–7.1%) for women and 12.0% (95% CI 11.9–12.1%) for men. This disparity was consistently observed throughout all phases of the pandemic, including the endemic phase of the disease. After adjusting for age, predominant viral genotype at illness onset and preexisting medical conditions, men had a 3.3% higher risk of severe manifestations when compared to women (RR = 1.033, 95% CI 1.032–1.034). Our research highlights the potential role of patients’ sex as a factor influencing pneumonia risk during and after the COVID-19 pandemic in Mexico. These findings may provide useful considerations for healthcare planning and policy development focused on addressing the impact of the disease on vulnerable populations.

Article URL: https://www.nature.com/articles/s41598-024-78200-0

Title

Mapping global public perspectives on mRNA vaccines and therapeutics

🤖 Abstract

Here is a simplified version of the abstract: A study examined how people viewed mRNA vaccines and therapeutics on social media during the COVID-19 pandemic, and found widespread negative attitudes and concerns about safety, effectiveness, and trustworthiness. The study compared online perspectives with official reports from the Vaccine Adverse Event Reporting System, revealing a lack of confidence in these treatments.

Abstract

The development and rollout of mRNA vaccines during COVID-19 marked a significant advancement in vaccinology, yet public hesitation to vaccination was prevalent, indicating the potential risk that future mRNA-based medical innovations will fail to be adopted. Utilizing a combined approach of large language models with manual validation and unsupervised machine learning, we conducted a social listening analysis to assess attitudes towards mRNA vaccines and therapeutics on Twitter from June 2022 to May 2023, contrasting online perspectives with data from the Vaccine Adverse Event Reporting System. Our findings reveal widespread negative sentiment and a global lack of confidence in the safety, effectiveness, and trustworthiness of mRNA vaccines and therapeutics, with frequent discussions of severe vaccine side effects, rumors, and misinformation. This underscores the need for targeted communication strategies to foster acceptance of medical treatments and strengthen public trust in order to enhance societal resilience to future health challenges.

Article URL: https://www.nature.com/articles/s41541-024-01019-3

Title

Decoding the nexus of stress tolerance, personal readiness for change, and psychological factors using PLS-SEM

🤖 Abstract

This study investigates how individual differences in stress tolerance, adaptability, and other factors affect their behavior and overall quality of life. It examines various psychological factors that influence human behavior using a sophisticated statistical method to discover the connections between these elements. The results show that self-esteem, others' perceptions, and world views are crucial in shaping an individual's level of stress tolerance, readiness for change, and overall well-being, with one factor (preference) acting as a significant mediator in this relationship.

Abstract

This research examines the intricate connections among three key elements: an individual’s ability to tolerate sources of stress, their willingness to adapt to new situations, and various psychological factors that influence human behavior. To analyze these relationships, the study employs a sophisticated statistical technique known as partial least squares structural equation modeling (PLS-SEM). A total of 327 Kazakhstan residents voluntarily participated in the study, comprising 84.6% women and 15.4% men, with ages ranging from 14 to 67 years old. “Stress Source Tolerance Scale” examined stress tolerance, “Personality Readiness Scale” measured readiness to change, and “Fatigue, Monotony, Satiety and Stress Questionnaire” investigated psychological states. The results indicate significant direct and indirect effects of self-esteem, others’ perceptions, and world perceptions on stress tolerance, readiness for change, and psychological states. Moreover, systematic preference has a significant mediating effect on the relationship between openness to change and psychological states. Results suggest that understanding these complex relationships may have implications for health, organizational effectiveness, and psychological well-being.

Article URL: https://www.nature.com/articles/s41599-024-04079-x

Title

Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice

🤖 Abstract

COVID-19 is a global health issue caused by a new coronavirus that can be life-threatening. The virus affects not only the lungs but also the central nervous system, which controls many functions in the body. Researchers are studying how the virus travels from the nose to the brain and why some people might develop severe symptoms or even die. Scientists have found that one possible way the virus enters the brain is through the olfactory nerve, a part of the brain's sensory system that smells and transmits information to other parts of the brain. When this nerve is damaged or absent, it may be harder for the virus to reach the brain. To test their hypothesis, researchers used mice with damaged olfactory nerves to see if they could prevent the virus from reaching the brain. The results showed that when these mice had healthy olfactory nerves, they were less likely to develop severe symptoms after being infected with COVID-19. This suggests that blocking the olfactory nerve pathway can help prevent the virus from invading the brain and causing illness in humans.

Abstract

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.

Article URL: https://www.nature.com/articles/s41598-024-78538-5

Title

Prone positioning is associated with increased insulin requirements in mechanically ventilated patients with COVID-19

🤖 Abstract

Here is a simplified version of the abstract: We studied patients who were on mechanical ventilation due to severe COVID-19, looking at how their blood sugar levels changed while they were being treated for hypoxia (lack of oxygen). We found that when these patients were moved from a flat position to an upright one (prone positioning), their blood sugar levels improved. But surprisingly, this improvement in blood sugar levels actually led to higher insulin doses being given, even though the patient's glucose control remained good. This was observed across different time periods and multiple groups of patients.

Abstract

Stress hyperglycaemia is common in critical illness. We have previously observed that increasing severity of respiratory failure in patients with severe COVID-19 is associated with increased insulin demand. Given previously reported direct effects of hypoxia on insulin action, we reasoned that rapid improvements in oxygenation following prone positioning may improve insulin sensitivity and increase risk of hypoglycaemia. A retrospective multi-centre service evaluation comparing blood glucose and insulin administration in patients with COVID-19 pneumonitis receiving prone mechanical ventilation, comparing the 16 h pre-prone and 16 h post-prone time periods. 155 patients were included in this analysis. Oxygenation improved significantly following prone positioning (change in SpO2/FIO2per hour prone: 3.01 ± 0.14,P< 0.0001). Glycaemic control was similar during the supine and prone study periods, and there were no hypoglycaemic events in the prone study period. Prone positioning was associated with an unexpected modest but significant increase in insulin requirements (mean difference in total insulin dose (IU): 8.32 ± 2.14,P< 0.001) that was robust to several sensitivity analyses, and could not be explained by changes in carbohydrate intake. We did not observe an increased rate of hypoglycaemia during prone ventilation and the adequacy of glycaemic control was comparable during the supine and prone study periods. Unexpectedly, prone ventilation was associated with an increase in insulin requirements despite significant improvement in hypoxaemia. Our findings support the safety of prone ventilation with respect to glycaemic control and identify a novel relationship between ventilation position and insulin requirements in critical illness.

Article URL: https://www.nature.com/articles/s41598-024-78904-3

Title

The effects of remdesivir on long-term symptoms in patients hospitalised for COVID-19: a pre-specified exploratory analysis

🤖 Abstract

A large group of patients in hospitals had symptoms from COVID-19 for several months, but some did not get better despite receiving treatment. The study looked at how well these patients were doing three months after the initial symptoms stopped. It found that treating them with a medication called remdesivir did not help much.

Abstract

BackgroundThere is an unmet need for treatment of long-term symptoms following COVID-19. Remdesivir is currently the only antiviral approved by the European Medicines Agency for hospitalised patients. Here, we report on the effect of remdesivir in addition to standard of care on long-term symptoms and quality of life in hospitalised patients with COVID-19 as part of the open-label randomised NOR-Solidarity trial (NCT04321616).MethodsA total of 185 patients were included in the main trial, of which 118 (60%) were randomised to either remdesivir (n = 42; 36%) or a post-hoc defined control group composed of patients who received standard of care alone or standard of care with hydroxychloroquine (n = 76; 64%). Participants were given quality of life surveys to fill out to gauge their self-reported health over time (the COPD assessment test, the EQ-5D-5L and the RAND SF-36).ResultsHere we show that after three months, patients treated with remdesivir do not show significant improvements in stated health compared to those who were not. There are self-reported symptoms of fatigue [mean remdesivir group 2.6 (standard deviation 1.5) v control 2.1 (1.6), 95% confidence interval(CI) −1.17 to 0.15, p = 0.129], shortness of breath [3.0 (1.7) v 2.1 (1.8), 95% CI −1.53 to 0.16, p = 0.110] and coughing [1.8 (1.6) v 1.2 (1.5), 95% CI −1.3 to 0.33, p = 0.237] 3 months after randomisation assessed via the COPD Assessment Test.ConclusionsOur findings indicate that treatment with remdesivir during hospitalisation does not provide any clinically relevant long-term benefit.

Article URL: https://www.nature.com/articles/s43856-024-00650-4

Title

Major alteration of lung microbiome and the host responses in critically ill COVID-19 patients with high viral load

🤖 Abstract

Patients on invasive mechanical ventilation are at higher risk of developing pneumonia due to COVID-19. A study analyzed lung microbiota and host immune responses in patients with confirmed SARS-CoV-2 infection who developed pneumonia. The researchers found that certain microorganisms were more common in patients with VAP, including Staphylococcus and Enterobacteriaceae. They also discovered changes in the metabolic activity of non-VAP patients compared to those with VAP, which may contribute to their increased susceptibility to developing VAP. The study suggests a link between respiratory microbiome alterations and ventilator-associated pneumonia, particularly in patients who have higher levels of SARS-CoV-2 in their respiratory samples. These findings can help inform management and prevention strategies for COVID-19 patients on mechanical ventilation.

Abstract

Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 h of intubation and again at 72 h post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably inStaphylococcusandEnterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients with higher SARS-CoV-2 viral loads in respiratory samples, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1β, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. These findings provide novel insights into the underlying mechanisms of VAP, with potential implications for management and prevention.

Article URL: https://www.nature.com/articles/s41598-024-78992-1

Title

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE

🤖 Abstract

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has shown reduced effectiveness in people with weakened immune systems, the cause of autoimmune diseases such as systemic lupus erythematosus (SLE). Scientists studied a group of patients who received the Wuhan-Hu-1 vaccine to understand why it was not working for them. The study found that these patients had weaker responses from certain parts of their immune system, which may be due to changes in these cells over time. It also showed that people with SLE were more likely to have strong responses against a specific type of protein on the virus, but this did not lead to protection against the full range of viruses. The study suggests that there are different types of B and T cell responses in people with SLE, which may help explain why some vaccines are effective while others are not.

Abstract

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD−CD27−‘double-negative (DN)’ DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.

Article URL: https://www.nature.com/articles/s41590-024-02010-9

Title

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial

🤖 Abstract

Assessment of the relationship between antibodies against COVID-19 vaccine and severity of illness. A study found that high levels of neutralizing antibodies at 4 weeks after vaccination were associated with better outcomes in COVID-19, including lower rates of severe critical cases. The study also looked at other antibody levels and found a correlation with protection against moderate COVID-19 as well as between severe and moderate disease.

Abstract

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90thpercentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.

Article URL: https://www.nature.com/articles/s41467-024-53727-y

Title

Assessment of knowledge and attitude of healthcare professionals towards Mpox in a Nigerian hospital

🤖 Abstract

Mpox is a disease that affects people worldwide and poses significant public health challenges. Research into healthcare workers' knowledge about the disease is limited. A study was conducted at Rivers State University Teaching Hospital in Nigeria to assess healthcare workers' understanding, awareness, attitudes, and factors related to mpox. A descriptive cross-sectional study design was used, with 227 healthcare professionals participating. The results showed that a high percentage (over 80%) of participants were female and single. Over 79% correctly identified mpox as a viral infection, but only 22.5% demonstrated good knowledge about the disease. Majority of healthcare workers acknowledged that mpox is a potential worldwide pandemic, with over 90% agreeing it could strain affected countries' healthcare systems. Despite this, healthcare workers generally have moderate to positive attitudes towards mpox, influenced by factors such as age, years of experience, professional qualification, and previous training on the disease. The study highlights the importance of targeted educational interventions in improving knowledge levels among healthcare professionals, but does not provide guidance on how to implement these interventions.

Abstract

Mpox is a zoonotic viral disease that presents significant public health challenges. Despite the pivotal role of healthcare workers, research on their knowledge and attitudes towards mpox is limited. This study aimed to assess healthcare workers’ knowledge, awareness and attitude regarding mpox as well as associated factors at Rivers State University Teaching Hospital in Nigeria. A descriptive cross-sectional study design was employed, utilizing a 34-item semi-structured questionnaire. Knowledge levels were categorized as good (> 70% score), fair (50–69%), or poor (< 50%), while attitudes were classified as positive (> 70% score), moderate (50–69%), or negative (< 50%). Statistical analyses included independent sample T-test, One-way Analysis of Variance, and Chi-square tests. Among a total of 227 healthcare professionals, majority were females (59%) and singles (54.2%). Over 79% correctly identified mpox as a viral infection, while 59.9% recognized its potential transmission through a monkey bite. Overall, 22.5% demonstrated good knowledge. Majority (61.7%) acknowledged the potential of mpox as a worldwide pandemic, with 89% agreeing it could strain affected countries’ healthcare systems. Healthcare workers exhibited moderate to positive attitudes towards mpox. Gender (Males, (p= 0.003), age (> 40 years (p= 0.008), years of experience (6–10 years; (p< 0.001), professional qualification (physicians, (p= 0.002), and previous mpox training (p< 0.001) significantly influenced knowledge levels, but no significant associations were found between demographic variables and attitudes. The study revealed a high level of awareness but low to fair knowledge among most participants. Healthcare professionals also demonstrated moderate to positive attitudes towards mpox. Factors such as gender, age, years of experience, professional qualification, and previous training on mpox influenced knowledge levels, but did not influence attitude in the study participants highlighting the importance of targeted educational interventions.

Article URL: https://www.nature.com/articles/s41598-024-79396-x

Title

Neutralization of SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 by human and murine sera

🤖 Abstract

Research has found that specific antibodies from a previous coronavirus (SARS-CoV-2) infection can offer increased protection against other related viruses. These findings show that individuals who had an initial COVID-19 infection or received a booster vaccine with the delta and BA.5.2 combination showed better neutralizing antibody responses than those who didn't experience breakthrough infections or were not vaccinated.

Abstract

We report SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 neutralizing antibody titers. They displayed increased immune evasion compared to JN.1, especially KP.1 and KP.3, for participants who experienced BF.7/BA.5.2 breakthrough infection or received bivalent (delta/BA.5) vaccine boosting. Second XBB sub-variants breakthrough infection enhanced the neutralization responses. HK.3-JN.1 RBD-heterodimer induced balanced and potent neutralizing responses against recently-circulating SARS-CoV-2 sub-variants in mice, supporting to replace the COVID-19 antigen containing JN.1 or its sub-variants.

Article URL: https://www.nature.com/articles/s41541-024-01016-6

Title

Sustainable Development Goals and wellbeing for resilient societies: shocks and recovery

🤖 Abstract

The 'decade of action' intended to accomplish 17 Sustainable Development Goals (SDGs) is facing significant challenges due to the COVID-19 pandemic. Our investigation shows that nearly 90% of SDGs were negatively affected, but there's hope for improvement with 66 targets benefiting from crisis-induced changes. To achieve this goal, a comprehensive approach and decisive leadership are necessary to guide an inclusive economic recovery while protecting the environment. The ongoing crises, environmental challenges, and conflicts require a proactive, deliberate, and well-informed strategy to steer the decade toward achieving the SDGs.

Abstract

The ‘decade of action’ intended to accomplish the ambitious 17 Sustainable Development Goals (SDGs) faces notable challenges. Our investigation into the impact of the COVID-19 crisis on SDG progress reveals important lessons for shaping effective policy interventions to ensure resilient societies and overall well-being. Through systematic mapping and a rapid review approach, our analysis reveals that nearly 90% of the SDGs, specifically 144 targets, were adversely affected by the COVID-19 pandemic. Yet, there is a glimmer of opportunity: 66 targets stand to gain from the crisis-induced transformations, provided that the right choices are made. Achieving this goal demands a comprehensive approach and decisive leadership to steer an inclusive economic recovery that also safeguards the environment while safeguarding the environment. The intricate interplay between the ongoing planetary and post-COVID-19 crises, environmental challenges, and conflicts underscores the need for a proactive, deliberate and well-informed approach, marked by collaborative decision-making, which is imperative for effectively steering the ‘decade of action’ toward achieving the SDGs. These complex challenges demand collective, decisive action, all with the overarching aim of securing a just and sustainable future for all.

Article URL: https://www.nature.com/articles/s41599-024-03973-8

Title

Immunogenicity of intraperitoneal and intranasal liposome adjuvanted VLP vaccines against SARS-CoV-2 infection

🤖 Abstract

Researchers created two types of vaccines against SARS-CoV-2 by using a virus that can't infect cells directly but causes an immune response when it tries to enter them. The first vaccine, L-SME-VLPs, had a special feature: its protein S is cut at the junction where two parts work together. The second vaccine, L-S′ME-VLPs, didn't have this feature. Both vaccines were harmless and triggered strong immunity in mice when given intraperitoneally (IP) or intranasally. The immune response in mice was measured by testing their blood for antibodies against SARS-CoV-2. The results showed that the second vaccine, L-S′ME-VLPs, induced stronger antibody production than the first vaccine, L-SME-VLPs. Most of the vaccinated mice had a higher level of neutralizing (VN) antibodies in their lungs when infected with the virus. VN antibodies are typically of specific types (IgG2a or IgG3). The mice also produced antibodies of other isotypes in their bronchoalveolar lavage fluids, which suggests that they were fighting the virus from different angles. Further testing of L-S′ME-VLPs through the nasal route is recommended to confirm its effectiveness and safety as a vaccine against SARS-CoV-2.

Abstract

Humans get SARS-CoV-2 infection mainly through inhalation; thus, vaccine that induces protective immunity at the virus entry site is important for early control of the infection. In this study, two anionic liposome (L)-adjuvanted VLP vaccines against SARS-CoV-2 were formulated. Baculovirus-Sf21 insect cell system was used for production of VLPs made of full-length S, M and E proteins. S protein of one vaccine (L-SME-VLPs) contained furin cleavage site at the S1/S2 junction, while that of another vaccine (L-S′ME-VLPs) did not. Both vaccines were innocuous and immunogenic when administered IP and IN to mice. Mice immunized IP with L-SME-VLPs/L-S′ME-VLPs (three doses, two-weeks intervals) had serum virus neutralizing (VN) antibodies (in falling order of isotype frequency): IgG3, IgA and IgG2a/IgG3, IgA and IgM, respectively. The L-S′ME VLPs vaccine induced significantly higher serum VN antibody titers than the L-SME-VLPs vaccine. All mice immunized IN with both vaccines had significant rise of VN antibodies in their bronchoalveolar lavage fluids (BALF). The VN antibodies in 67% of immunized mice were Th1- isotypes (IgG2a and/or IgG2b); the immunized mice had also other antibody isotypes in BALF. The intranasal L-S′ME-VLPs should be tested further step-by-step towards the clinical use as effective and safe vaccine against SARS-CoV-2.

Article URL: https://www.nature.com/articles/s41598-024-79122-7

Title

Unraveling the protective genetic architecture of COVID-19 in the Brazilian Amazon

🤖 Abstract

Researchers studied how genetic factors contribute to a person's risk of getting very sick or not at all from COVID-19 despite extensive research during the pandemic. They analyzed data from 124 patients who were categorized into two groups based on their condition and found four genetic variants that may help protect against severe illness. Their study highlights the importance of understanding how genetic differences affect people living in diverse regions, particularly those with rare alleles.

Abstract

Despite all the efforts acquired in four years of the COVID-19 pandemic, the path to a full understanding of the biological mechanisms involved in this disease remains complex. This is partly due to a combination of factors, including the inherent characteristics of the infection, socio-environmental elements, and the variations observed within both the viral and the human genomes. Thus, this study aimed to investigate the correlation between genetic host factors and the severity of COVID-19. We conducted whole exome sequencing (WES) of 124 patients, categorized into severe and non-severe groups. From the whole exome sequencing (WES) association analysis, four variants (rs1770731 inCRYBG1, rs7221209 inDNAH17, rs3826295 inDGKE, and rs7913626 inCFAP46) were identified as potentially linked to a protective effect against the clinical severity of COVID-19, which may explain the less severe impact of COVID-19 on the Northern Region. Our findings underscore the importance of carrying out more genomic studies in populations living in the Amazon, one of the most diverse from the point of view of the presence of rare and specific alleles. To our knowledge, this is the first WES study of admixed individuals from the Brazilian Amazon to investigate genomic variants associated with the clinical severity of COVID-19.

Article URL: https://www.nature.com/articles/s41598-024-78170-3

Title

Assessing acute kidney injury risk after COVID vaccination and infection in a large cohort study

🤖 Abstract

Acute kidney injury (AKI) after COVID-19 infection affects vaccine risk-benefit evaluations and vaccine hesitancy, but researchers investigated the relationship between COVID-19 vaccination and AKI incidence. A large study tracked over 7 million people's exposure to COVID-19, comparing their likelihood of developing AKI. The results showed that people who got vaccinated had a lower risk of AKI (0.66%) compared to those who contracted the virus (4.88%). The more severe COVID-19 infection was associated with a significantly higher risk of AKI than vaccination.

Abstract

Acute kidney injury (AKI) has been noticed after both COVID-19 vaccination and infection, affecting risk-benefit evaluations and vaccine hesitancy. We conducted a large-scale N3C cohort study to compare AKI incidence following COVID-19 vaccination and infection. Participants from December 2020 to August 2023 were divided into two groups based on their initially observed COVID-19 antigen exposure: COVID-19 vaccination group (n= 2,953,219) and COVID-19 infection group (n= 3,616,802). AKI was defined by diagnostic codes and serum creatinine changes within a 30 day follow-up window after exposure. The absolute risk of AKI was 0.66% in the vaccination group versus 4.88% in the infection group. After adjusting for various confounders, COVID-19 infection was associated with a significantly higher risk of AKI than COVID-19 vaccination (aHR = 10.31,P< 0.001). Our study reveals that COVID-19 vaccination is associated with a significant lower AKI risk compared to COVID-19 infection.

Article URL: https://www.nature.com/articles/s41541-024-00964-3

Title

Detection of SARS-CoV-2 in wastewater as an earlier predictor of COVID-19 epidemic peaks in Venezuela

🤖 Abstract

Wastewater-based epidemiological surveillance was a successful tool for detecting COVID-19 outbreaks in Venezuela by analyzing viral RNA from collected wastewater and comparing it with reported cases of the disease. The method helped identify connections between wastewater samples and reported cases up to six days after collection, suggesting that wastewater surveillance could be an early warning system for SARS-CoV-2 outbreaks in areas where public health monitoring is limited.

Abstract

Wastewater-based epidemiological surveillance has proven to be a useful and cost-effective tool for detecting COVID-19 outbreaks. Here, our objective was to evaluate its potential as an early warning system in Venezuela by detecting SARS-CoV-2 RNA in wastewater and its correlation with reported cases of COVID-19. Viral RNA was concentrated from wastewater collected at various sites in Caracas (northern Venezuela), from September 2021 to July 2023, using the polyethylene glycol (PEG) precipitation method. Viral quantification was performed by RT-qPCR targeting the N1 and ORF1ab genes. A significant association (p< 0.05) was found between viral load in wastewater and reported cases of COVID-19 up to six days after sampling. During the whole study, two populated areas of the city were persistent hotspots of viral infection. The L452R mutation, suggestive of the presence of the Delta variant, was identified in the only sample where a complete genomic sequence could be obtained. Significant differences (p< 0.05) between the physicochemical conditions of the wastewater samples positive and negative for the virus were found. Our results support proof of concept that wastewater surveillance can serve as an early warning system for SARS-CoV-2 outbreaks, complementing public health surveillance in those regions where COVID-19 is currently underreported.

Article URL: https://www.nature.com/articles/s41598-024-78982-3

Title

A case-control study of reaction time deficits in a 3D virtual reality in patients with Post-COVID syndrome

🤖 Abstract

A large number of people report Post-COVID symptoms after COVID-19, but there are no objective tests to diagnose them. A study used virtual reality to test how well patients with Post-COVID syndrome (PCS) can see and respond to visual stimuli compared to healthy individuals. The researchers found that PCS patients performed worse in a virtual reality test of reaction time than healthy people, especially when it came to seeing 3D objects. When controlling for other factors like age and sex, the differences in reaction time were still significant. Some specific findings include: - Patients with PCS were slower and more inaccurate at a certain level of visual intensity (disparity) - The speed and accuracy of patients with PCS improved as they aged - Women's performance on this task was better than men's The researchers think that the virtual reality test provided some clues about why people with PCS might be experiencing symptoms. They believe it could lead to new ways of diagnosing and treating PCS.

Abstract

Following the Coronavirus disease 2019 (COVID-19) pandemic, a large number of people continue to report Post-COVID symptoms (PCS). A wide variety of symptoms are described, including fatigue, post-exertional malaise and cognitive impairment. However, adequate objective diagnostic tests for PCS are not yet available. Since the neurotropism of SARS-CoV-2 could be a possible factor for cognitive impairment, the aim of this study was to clarify whether visual reaction time (RT) in a stereoscopic setting can be a marker in PCS diagnostics. The Virtual-Reality-Oculomotor-Test-System (VR-OTS) was used testing binocular vision in 9 gaze directions via stereoscopic stimuli displayed in a virtual reality (VR)-environment (disparity: 275″, 550″, 1100″) in 179 individuals: 130 patients with PCS and 49 healthy controls. The results from the generalized linear models indicated that both group membership (PCS vs. control) and covariates (age and sex) yielded statistically significant different RT across the models. Accounting for the effect of covariates a statistically significant difference of RT was observed between patients with PCS and controls (disparity 275″ p-value = 0.001; 550″ p-value = 0.001; 1100″ p-value = 0.003). Patients with PCS performed worse in RT in all gaze directions, respectively. Adjusting for the influence of covariates, correct responses (CR) differed significantly between patients with PCS and controls (disparity 275″ p-value < 0.001; 550″ p-value = 0.003; 1100″ p-value = 0.019). Statistically significant effects of covariates on RT were observed for sex (disparity 275″ p-value = 0.047; 550″ p-value = 0.012; 1100″ p-value = 0.005) and age (disparity 275″ p-value < 0.001; 550″ p-value < 0.001; 1100″ p-value < 0.001). However, regarding covariates, no significant effects were found for CR, except for age at disparity 275″ (p-value = 0.035). The present data suggested that the mentioned variables uniquely contributed to explain the variation of the response variable (RT, CR). RT and CR detecting 3D-stimuli in a virtual 3D- environment might offer novel functional diagnostic approaches in PCS.

Article URL: https://www.nature.com/articles/s41598-024-76827-7

Title

Visualizing the human olfactory projection and ancillary structures in a 3D reconstruction

🤖 Abstract

Here's a simplified abstract that a young person can understand: Scientists created a 3D model of how smell is processed in the human brain by scanning a dead body and staining different parts with special dyes. They then looked at pictures of these stained parts to identify six specific structures, which they used to train computers to automatically recognize them on many other sections of the same body part. The computers were able to build an accurate picture of how much each structure is in every part of the body, giving scientists a better understanding of how smell works in humans compared to mice.

Abstract

Visualizing in 3D the histological microanatomy of the human olfactory projection from the olfactory mucosa in the nasal cavity to the olfactory bulbs in the cranial cavity necessitates a workflow for handling a great many sections. Here, we assembled a 3D reconstruction of a 7.45 cm3en-blocspecimen extracted from an embalmed human cadaver. A series of 10 µm coronal sections was stained with quadruple fluorescence histology and scanned in four channels. A trained anatomist manually segmented six structures of interest in a subset of the sections to generate the ground truth. Six convolutional neural networks were then trained for automatic segmentation of these structures in 1234 sections. A high-performance computing solution was engineered to register the sections based on the fluorescence signal and segmented structures. The resulting 3D visualization offers several novel didactic opportunities of interactive exploration and virtual manipulation. By extrapolating manual counts of OSNs in a subset of sections to the calculated volume of the envelope of the entire olfactory epithelium, we computed a total of ~2.7 million OSNs in the specimen. Such empirically derived information helps assess the extent to which the organizational principles of the human olfactory projection may differ from those in mice.

Article URL: https://www.nature.com/articles/s42003-024-07017-4

Title

Loss of resources and gambling during the COVID-19 pandemic: a three-wave longitudinal study

🤖 Abstract

This study looks at how the COVID-19 pandemic affected people who gamble in person. It surveyed 585 Polish gamblers before the pandemic to understand their behaviour, preferences, and financial situations. The results showed that online gambling increased significantly during lockdowns and reduced when restrictions eased. Gamblers who engaged more in land-based activities had greater losses due to resource depletion. Those with limited resources were at higher risk of problems. Heavy gamblers were also more likely to experience issues even if they had stable gambling habits before the pandemic. The study suggests that factors such as frequency and amount of gaming can have a strong impact on financial losses, especially when combined with other stressors like pandemic-related restrictions.

Abstract

This study is based on the Conservation of Resources theory and investigates the impact of the COVID-19 pandemic and associated resource loss on gambling behaviour among Polish gamblers. The study surveyed 585 individuals engaged in land-based gambling before the pandemic. Participants completed computer-assisted web interviews, responding to questions regarding land-based and online gambling frequencies, the Problem Gambling Severity Index, and the Inventory of Loss of Resources in Pandemics. The findings revealed significant shifts in gambling behaviour due to pandemic-related restrictions. Land-based gambling declined during lockdowns and the third wave of the study, while online gambling surged as gamblers transitioned from land-based venues. Gamblers tended to return to land-based options as restrictions eased. Over consecutive waves, participants reported decreasing resource loss levels. Significantly, resource loss was influenced by gambling frequency rather than vice versa. Both types of gambling experienced parallel declines at the beginning of the pandemic, which subsided as the new situation became normalised. Players engaging more in gambling experienced more significant resource losses during the pandemic. Those with more resources at the pandemic’s onset adapted more readily, whereas individuals with limited resources faced resource loss. Conclusions Even with stable gambling levels, heavy gamblers at baseline were at higher risk for issues. The dynamics between resource loss and gambling and problem gambling supported the resource loss spiral concept.

Article URL: https://www.nature.com/articles/s41598-024-78866-6

Title

mRNA delivery enabled by metal–organic nanoparticles

🤖 Abstract

mRNA therapeutics are on the verge of revolutionizing disease prevention and treatment, but their current delivery systems face challenges like limited organ tropism and inflammation from cationic components. A new platform aims to overcome these issues by creating nanoparticles that can safely deliver mRNA to various organs in the body. This innovation uses a special type of nanoparticle that is non-cationic and biocompatible, allowing it to easily pass through the body's tissues without causing harm. The researchers screened various combinations of components and found a range of stable, safe, and effective nanoparticles with excellent gene editing capabilities. These nanoscale particles can be administered intravenously and have shown promise in the brain, liver, and kidney for delivering mRNA therapeutics, opening up new possibilities for treating diseases.

Abstract

mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, current mRNA delivery platforms face some challenges, including limited organ tropism for nonvaccine applications and inflammation induced by cationic nanoparticle components. Herein, we address these challenges through a versatile, noncationic nanoparticle platform whereby mRNA is assembled into a poly(ethylene glycol)-polyphenol network stabilized by metal ions. Screening a range of components and relative compositional ratios affords a library of stable, noncationic, and highly biocompatible metal–organic nanoparticles with robust mRNA transfection in vitro and in mice. Intravenous administration of the lead mRNA-containing metal–organic nanoparticles enables predominant protein expression and gene editing in the brain, liver, and kidney, while organ tropism is tuned by varying nanoparticle composition. This study opens an avenue for realizing metal–organic nanoparticle-enabled mRNA delivery, offering a modular approach to assembling mRNA therapeutics for health applications.

Article URL: https://www.nature.com/articles/s41467-024-53969-w

Title

Transcutaneous electrical nerve stimulation for fibromyalgia-like syndrome in patients with Long-COVID: a pilot randomized clinical trial

🤖 Abstract

Here is a simplified version of the abstract: Researchers studied how a device that sends electrical impulses to nerves (TENS) can help people with fibromyalgia-like symptoms such as chronic pain, fatigue, and gait problems. They gave 25 participants either a high-dose or low-dose version of this TENS device for four weeks. The results showed that the participants who received the higher dose had better symptoms at the end of the study compared to those who didn't get it. They also improved their walking abilities, such as stride time and cadence.

Abstract

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3–5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease in BPI-I compared to the PG (mean difference = 2.61,p= 0.008), and improved in gait parameters including stride time (4-8%, test condition dependent), cadence (4-10%, depending on condition), and double-support phase (12% in dual-task) when compared to baseline. A sub-group meeting the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria undergoing high-dose TENS showed GFI improvement at 4-weeks from baseline (mean change = 6.08,p= 0.005). Daily TENS therapy showed potential in reducing functional interference from pain, fatigue, and gait alterations in long-COVID individuals. The study’s limited power could affect the confirmation of certain observations. Extending the intervention period may improve treatment effectiveness.

Article URL: https://www.nature.com/articles/s41598-024-78651-5

Title

Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies

🤖 Abstract

Here's a simplified abstract: Researchers have been working on developing new treatments to combat COVID-19 by targeting the virus itself rather than just its symptoms. They've discovered three potential compounds that can stop the coronavirus from replicating inside cells, and these compounds also seem effective against other coronaviruses. The researchers used an existing library of compounds to test them and found promising results in lab tests and animal studies. This work could help advance research into new treatments for COVID-19 and potentially other viral infections.

Abstract

The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis. The three compounds are (1) the nucleotide analog cordycepin, (2) a benzothiozole analog, and (3) an acyldepsipeptide analog initially developed as part of a campaign to target the mitochondrial ClpP protease. These compounds demonstrated dose-dependent efficacy against multiple coronaviruses, including SARS-CoV-2, effectively inhibiting viral replication in vitro as well as in lung organoids. Notably, the compounds also showed efficacy against SARS-CoV-2 delta and omicron strains. As part of this work, we developed a BSL2-level cell-integrated SARS-CoV-2 replicon, which could serve as a valuable tool for high-throughput screening and studying intracellular viral replication. Our study should aid in the advancement of antiviral drug development efforts.

Article URL: https://www.nature.com/articles/s42003-024-07143-z

Title

When fatigue and cognitive impairment persist- a neurological follow-up-study in patients with Post-COVID syndrome

🤖 Abstract

A study was conducted to look at how well people who have had COVID-19 can recover from the condition, which affects their mood, sleep quality, and overall well-being. The study looked at the condition's impact on patients 6 months after they first got sick with COVID-2. Researchers studied how many of these patients improved over time, what aspects of their lives affected this improvement, and whether people recovered fully or not. They also checked how much fatigue, concentration, and memory were impacted by the condition. The study found that a significant number of people who had initially felt better for some period after getting sick with COVID-2 continued to experience symptoms over time. People with positive improvements in their lives experienced an increase in quality of life but not in their performance on tests or their energy levels. On the other hand, people whose symptoms didn't improve at all experienced a gradual decline in their condition and were unable to return to normal activities after a year or more had COVID-2 gone.

Abstract

Considering the relevance for patients, economics and public health data about the course of the neurological Post-COVID Syndrome (PCS) are urgently needed. In this study 94 PCS patients (73% female, age in median 49 years) were examined in median 9.4 (T1) and for a second time 14 months (T2) after mild to moderate SARS-CoV-2 infection. Mood, sleep quality and health related quality of life (QoL) were evaluated via structured anamnesis and self-report questionnaires; attention, concentration and memory via psychometric tests. 47% of the patients reported an improvement of their symptoms over time, but only 12% full recovery. 4% noticed deterioration and 49% no change. Main disturbances at both time points were fatigue, deficits in concentration and memory. In patients with perceived improvement QoL significantly increased between T1 and T2, although their test performance as well as the fatigue score remained unchanged. In patients with persisting impairment QoL, fatigue scores and psychometric test results did not change significantly. Abnormal psychometric tests were more frequent at both time points in the group without improvement. But, significant fatigue and cognitive impairment persisted for more than 1 year after SARS-CoV-2 infection in both groups.

Article URL: https://www.nature.com/articles/s41598-024-78496-y

Title

Effect of carbon black and silicon dioxide nanoparticle exposure on corona receptor ACE2 and TMPRSS2 expression in the ocular surface

🤖 Abstract

The COVID-19 pandemic has led to a global health crisis. A specific strain called coronavirus causes symptoms like eye problems and is spread by tiny particles in the air we breathe. These particles can affect how our eyes work. Research found that some of these tiny particles can make us sick, while others might even help prevent it. Tiny particles from traffic emissions can damage the body's receptors on the eyes. A common particle used to study this damage was silica (SiO2), which is often found in sand and car exhaust. Scientists also looked at a type of fiber called carbon black (CB) that comes from old cars and factories. They tested how these particles affect cells on the inside of our eyes, like corneal and conjunctival cells, as well as nearby tissues. They measured changes in the levels of certain proteins in the bloodstream using special tests. In a separate study, they looked at what happens when tiny particles are applied to the surface of our eyes. This helped them understand how COVID-19 might affect the body's eye health. The results showed that some types of silica (SiO2) and carbon black (CB) can damage corneal cells more than others. Silica particles were found to increase inflammation in the blood, while carbon black particles increased levels of a protein called tumor necrosis factor-alpha (TNF-α).

Abstract

The Coronavirus disease 2019 (COVID-19) pandemic has led to a global health crisis, including ocular symptoms, primarily targeting the Angiotensin-Converting Enzyme 2 (ACE2) receptor. PM2.5 air pollution may increase infection risk by altering ACE2 expression. Silicon Dioxide (SiO2) and carbon black (CB), major components of PM2.5 from sands and vehicle emissions, were studied for their effects on ACE2 and Transmembrane Protease Serine 2 (TMPRSS2) expression in corneal and conjunctival cells, and ocular tissues. Human corneal epithelial cells (HCECs) and conjunctival epithelial cells (HCjECs) were exposed to nanoparticles (NPs) for 24 hours, assessing viability via WST-8 assay. TNF-α, IL-6, and IL-1β levels in the medium were measured. An in vivo rat study administered NPs via eye drops, with Rose Bengal staining to evaluate damage. ACE2, TMPRSS2, and Angiotensin II (AngII) protein expressions were quantified by Western blot. ACE2 expression in HCjECs increased with NP exposure, while it decreased in HCECs. CB exposure increased TNF-α, IL-6, and IL-1β levels in HCECs. In vivo, corneal exposure to CB decreased ACE2 expression, whereas conjunctival exposure to SiO2increased ACE2 expression. These changes suggest that SiO2 exposure may increase the risk of COVID-19 through the ocular surface, while CB exposure may decrease it.

Article URL: https://www.nature.com/articles/s41598-024-78518-9

Title

Predictive modeling of COVID-19 mortality risk in chronic kidney disease patients using multiple machine learning algorithms

🤖 Abstract

A new disease called COVID-19 has affected many people worldwide, especially those with chronic kidney disease (CKD). If someone has CKD and is infected with COVID-19, they are more likely to die than others. A team of scientists created a predictive model that helps identify which patients at high risk of death from COVID-19 due to their CKD will live longer if treated properly. The researchers analyzed the data of 219 patients who had COVID-19 and studied how well different variables predicted mortality rates, such as blood tests and other medical information. They found a simple formula that can be used to predict which patients are at high risk of death from COVID-19 due to their CKD.

Abstract

The coronavirus disease 2019 (COVID-19) has a significant impact on the global population, particularly on individuals with chronic kidney disease (CKD). COVID-19 patients with CKD will face a considerably higher risk of mortality than the general population. This study developed a predictive model for assessing mortality in COVID-19-affected CKD patients, providing personalized risk prediction to optimize clinical management and reduce mortality rates. We developed machine learning algorithms to analyze 219 patients’ clinical laboratory test data retrospectively. The performance of each model was assessed using a calibration curve, decision curve analysis, and receiver operating characteristic (ROC) curve. It was found that the LightGBM model showed the most satisfied performance, with an area under the ROC curve of 0.833, sensitivity of 0.952, and specificity of 0.714. Prealbumin, neutrophil percent, respiratory index in arterial blood, half-saturated pressure of oxygen, carbon dioxide in serum, glucose, neutrophil count, and uric acid were the top 8 significant variables in the prediction model. Validation by 46 patients demonstrated acceptable accuracy. This model can serve as a powerful tool for screening CKD patients at high risk of COVID-19-related mortality and providing decision support for clinical staff, enabling efficient allocation of resources, and facilitating timely and targeted management for those who need the relevant interference urgently.

Article URL: https://www.nature.com/articles/s41598-024-78498-w

Title

Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Researchers have created a new type of vaccine called nanovaccines that use tiny particles made of DNA (a building block of life) to fight off viruses like SARS-CoV-2. However, these nanoparticles are different from the actual virus and their shape and size are not perfectly matched. To improve this, scientists came up with a special way to display viral proteins on the surface of these nanoparticles using tiny pieces of DNA called DNA origami. By doing so, they can control how many copies of the protein clusters (like patterns) are displayed on each nanoparticle's surface. This allows them to optimize the immune response from B cells and T cells that recognize the virus. The researchers tested their new nanovaccines in mice and found that they were more effective at activating these immune cells than traditional vaccines or antiviral medications. The results suggest that multivalent (many-antigen) displays of viral proteins like RBD on nanoparticles may be a powerful way to create more effective treatments against future pandemics.

Abstract

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.

Article URL: https://www.nature.com/articles/s41467-024-53937-4

Title

A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2

🤖 Abstract

**Abstract** Researchers have discovered a new type of protein that can help protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is because some parts of this protein can escape detection by our immune system, allowing SARS-CoV-2 to spread more easily in vaccinated individuals. The researchers tested three versions of the protein and found they work better than a version that was already known to be effective. These new proteins are promising candidates for making a vaccine against SARS-CoV-2 that can protect against many different variants of the virus.

Abstract

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants. Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury. Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs. This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies.

Article URL: https://www.nature.com/articles/s41392-024-02007-8

Title

Pulmonary diffusing capacity among individuals recovering from mild to moderate COVID-19: a cross-sectional study

🤖 Abstract

Impaired lung function (DLCO) in people who have had severe COVID-19 has been reported, but most cases of long COVID are not severe enough to cause this impairment. We studied a large group of adults with long COVID recovering from mild to moderate illness and found that 17% had impaired DLCO. Certain factors were associated with this condition, including being female, having significant breathing difficulties (moderate-severe), and high levels of cigarette smoking. A lower BMI was also linked to impaired DLCO. These findings suggest that clinicians should be aware of the possibility of impaired DLCO in patients recovering from mild COVID-19 and use self-reported symptoms, such as severe breathing difficulties, to guide further assessment.

Abstract

Impaired pulmonary diffusing capacity for carbon monoxide (DLCO) following COVID-19 has been consistently reported among individuals recovering from severe-critical infection. However, most long COVID cases follow non-severe COVID-19. We assessed DLCO among individuals with long COVID recovering from mild to moderate acute illness. A cross-sectional study of adults with long COVID, assessed at a COVID recovery clinic > 3 months following the onset of acute infection, during 2020–2021. Participants subjectively ranked their dyspnea severity based on its impact on their daily living and underwent comprehensive pulmonary function testing (PFT). Clinical correlates for impaired DLCO (defined as < 80%) were assessed using multivariable logistic regression models. A total of 458 individuals, their mean age 45 (SD 16) and 246 (54%) of whom are women, were evaluated at an average of ~ 4 months following acute COVID-19. The most frequent PFT impairment was reduced DLCO, identified among 67 (17%) of the cohort. Clinical correlates of impaired DLCO included women (odds ration [OR] 3.64, 95% confidence interval [CI] 1.78–7.45,p< 0.001), cigarette smoking (OR 2.25, 95% CI 1.14–4.43,p= 0.019), and moderate-severe dyspnea (OR 2.77, 95% CI 1.39–5.50,p= 0.004). BMI inversely correlated with DLCO (OR 0.90, 95% CI 0.85–0.96 per 1 unit,p= 0.002). Impaired DLCO was not uncommon among individuals recovering from mild to moderate COVID-19. Women are at a greater risk, and subjective dyspnea correlated with impaired DLCO. Clinicians can rely on self-reported significant dyspnea to guide further assessment.

Article URL: https://www.nature.com/articles/s41598-024-74404-6

Title

Comparative assessment of a COVID-19 vaccine after technology transfer to Iran from critical quality attributes to clinical and immunogenicity aspects

🤖 Abstract

Here is a simplified version of the abstract: During the COVID-19 pandemic, international pharmaceutical companies developed global manufacturing networks for COVID-19 vaccines to share with countries like Iran. This study looked at how two similar vaccine types (Soberana Plus and PastoCovac Plus) were transferred from Cuba to Iran and tested their safety and effectiveness before and after transfer. The researchers compared the two vaccines side by side, checking things like what was in them, how they worked, and if people getting vaccinated caused any problems. They also checked for differences in things that could make someone get sick again or recover quickly. After comparing both vaccines, the results showed that they were similar and safe to use, with no significant difference in how well they protected against COVID-19.

Abstract

During COVID-19 pandemic, international pharmaceutical companies put effort to build global manufacturing networks for vaccines. Soberana Plus vaccine, a recombinant protein based vaccine (RBD dimer), with the trade name of PastoCovac Plus in Iran, is based on a protein subunit platform in Cuba and completed preclinical and toxicological assessments. This study aimed at presenting the steps of vaccine technology transfer from Cuba to Iran. This study provides the first practical comparability results in Iran to ensure the quality, safety and efficacy of a protein subunit vaccine against COVID-19 after a successful technology transfer from Cuba. PastoCovac Plus was transferred to Iran at the formulation stage. The assessment of the active ingredient pharmaceutical (API) was achieved through physicochemical and clinical data collection and tests to assure if there was any adverse impact on the vaccination results. In order to assess the quality of the vaccine product after technology transfer, we sought different properties including regulatory features, physicochemical quality, vaccine potency and stability as well as its immunogenicity and safety. Following the evaluation of the clinical quality attributes (CQAs) based on the standard protocols, the results showed that the two vaccines are highly similar and comparable, with no considerable effect on safety or efficacy profiles. The CQAs were all in the acceptance limits in terms of safety and efficacy as well as clinical evaluation results. The immunogenicity evaluation also confirmed no significant differences between the vaccines regarding reinfection (P = 0.199) or vaccine breakthrough (P = 0.176). Furthermore, the level of anti-spike and neutralizing antibodies in the both vaccine groups was not significantly different indicating the equality of performance between the two vaccines. According to the results of the quality and clinical assessment of this study, we achieved an acceptable quality attributes and acceptant limits in terms of safety and efficacy of the vaccines pre and post technology transfer.

Article URL: https://www.nature.com/articles/s41598-024-77331-8

Title

Data normalization of plasma miRNA profiling from patients with COVID-19

🤖 Abstract

When analyzing coronavirus disease 2019 (COVID-19) with reverse-transcription quantitative polymerase chain reaction (RT-qPCR), it's essential to use a reliable and stable gene as an endogenous reference for microRNA (miRNA) expression. However, no single universally suitable gene exists. In this study, researchers used RNA sequencing techniques to identify the best miRNAs for normalizing miRNA expression in patients with COVID-19 compared to healthy volunteers or those with mild versus severe cases. They found four promising candidates: hsa-miR-34a-3p, hsa-miR-194-3p, hsa-miR-17-3p, and hsa-miR-205-3p. Only one of these, miR-205-3p, met the criteria for being a stable endogenous normalizer in both COVID-19 groups.

Abstract

When using the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) technique for quantitative assessment of microRNA (miRNA) expression, normalizing data using a stable endogenous gene is essential; however, no universally adequate reference gene exists. Therefore, in this study, we aimed to determine, via the RNA-Seq technique, the most adequate endogenous normalizer for the expression assessment of plasma miRNAs in patients with coronavirus disease 2019 (COVID-19). Two massive sequencing procedures were performed (a) to identify differentially expressed miRNAs between patients with COVID-19 and healthy volunteers (n =12), and (b) to identify differentially expressed miRNAs between patients with severe COVID-19 and those with mild COVID-19 (n =8). The endogenous normalizer candidates were selected according to the following criteria: (1) the miRNA must have a fold regulation = 1; (2) the miRNA must have ap-value > 0.990; and (3) the miRNAs that were discovered the longest ago should be selected. Four miRNAs (hsa-miR-34a-3p, hsa-miR-194-3p, hsa-miR-17-3p, and hsa-miR-205-3p) met all criteria and were selected for validation by RT-qPCR in a cohort of 125 patients. Of these, only hsa-miR-205-3p was eligible endogenous normalizers in the context of COVID-19 because their expression was stable between the compared groups.

Article URL: https://www.nature.com/articles/s41598-024-75740-3

Title

Characterization of a SARS-CoV-2 Omicron BA.5 direct-contact transmission model in hamsters

🤖 Abstract

SARS-CoV-2 infection in animals has evolved rapidly, making it difficult to find suitable models for studying new treatments. Researchers used Syrian hamsters as the test subjects because they are highly susceptible to SARS-CoV-2 and experience tissue damage similar to human lungs when infected. To develop a model that would allow scientists to study different interventions against viral variants like Omicron BA.5, researchers set up a direct-contact transmission system between donor and recipient hamsters. They found that using an inoculum of 103 or 104 TCID50 in low-volume drops led to consistent infection and shedding in both male and female hamsters. To ensure consistent transmission, the researchers chose specific times and durations for co-housing donor and recipient hamsters. They observed that the virus was shed more easily by males than females. The study also found that males were infected at lower viral loads and experienced limited weight loss compared to females. By replicating the SARS-CoV-2 Omicron BA.5 infection in hamsters, researchers developed a robust model for studying interventions against new viral variants like this one.

Abstract

As SARS-CoV-2 continues to evolve antigenically to escape vaccine- or infection-induced immunity, suitable animal models are needed to study novel interventions against viral variants. Syrian hamsters are often used because of their high susceptibility to SARS-CoV-2 and associated tissue damage in the respiratory tract. Here, we established a direct-contact transmission model for SARS-CoV-2 Omicron BA.5 in hamsters. First, we determined whether 103or 104TCID50in a low-volume inoculum led to reproducible infection and viral shedding in male and female hamsters. Next, we determined the optimal co-housing timing and duration between donor and recipient hamsters required for consistent direct-contact transmission. Finally, we compared viral loads and histopathological lesions in the respiratory tissues of donor and recipient hamsters. Intranasal inoculation of hamsters with 103TCID50and 104TCID50Omicron BA.5 in 10 µl per nostril led to reproducible infection. Viral loads in the throat measured by RT-qPCR were comparable between male and female hamsters. Notably, the shedding of infectious virus was significantly higher in male hamsters. Compared to SARS-CoV-2 D614G, Omicron BA.5 infection reached lower viral loads, had a delayed peak of virus replication, and induced limited body weight loss. To ensure consistent direct-contact transmission from inoculated donor hamsters to naïve recipients, a co-housing duration of 24 h starting 20 h post-infection of the donors was optimal. We detected mild inflammation in the respiratory tract of donor and recipient hamsters, and viral loads were higher and peaked earlier in donor hamsters compared to recipient hamsters. Taken together, we developed a robust Omicron BA.5 direct-contact transmission model in hamsters, that provides a valuable tool to study novel interventions.

Article URL: https://www.nature.com/articles/s44298-024-00061-1

Title

Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis

🤖 Abstract

Identifying specific regions of viral proteins in immune cells is important for understanding how the body responds to infection. This study developed a new method for identifying these regions from memory T cells, reducing the time and cost involved in this process. They used a combination of techniques, including using yeast that display peptides on its surface, to quickly find which regions of viral proteins are most immunogenic. The study focused on SARS-CoV-2 and found that many people's immune systems produce antibodies against certain parts of the virus. This suggests that these antibodies could help protect against future infections with different strains of the virus.

Abstract

Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants.

Article URL: https://www.nature.com/articles/s42003-024-07048-x

Title

Mesenchymal stem cell-derived extracellular vesicles reduce inflammatory responses to SARS-CoV-2 and Influenza viral proteins via miR-146a/NF-κB pathway

🤖 Abstract

The risk of severe disease from two viruses, such as SARS-CoV-2 and influenza, poses a concern for global public health each year. Researchers have found that tiny particles called extracellular vesicles (EVs) derived from stem cells can help reduce inflammation caused by viral infections. These EVs are particularly useful because they contain anti-inflammatory proteins that can calm down the immune system's response to an infection. However, more research is needed to understand how these EVs work in combination with viruses like SARS-CoV-2 and influenza. In one part of the study, scientists found that lung cells were more likely to die or not grow properly when they were infected by both viruses simultaneously. They also discovered a type of protein called miR-146a that helps regulate inflammation in these cells. When this protein is present in EVs from stem cells, it can help counteract the effects of inflammation and promote healing. The researchers found that the microRNA (miR-146a) plays a key role in suppressing inflammation by targeting specific parts of a signaling pathway called NF-κB. This pathway helps fight off infection but also causes inflammation when it's active too long. The study also discovered that people with type 2 diabetes may have trouble using these EVs to treat their condition because they contain less miR-146a and can't effectively target the NF-κB pathway, leading to more inflammation.

Abstract

The risk of severe disease caused by co-infection with SARS-CoV-2 and influenza virus (IAV) raises an annual concern for global public health. Extracellular vesicles (EV) derived from mesenchymal stem cells (MSC) possess anti-inflammatory properties that can attenuate the inflammatory cytokine levels induced by viral infection. However, the effects of MSC-EV treatment on SARS-CoV-2 and IAV co-infection have not been elucidated. In the present study, we co-induced lung epithelial cells (EpiC) with SARS-CoV-2 Spike protein (S) and H1N1 influenza viral HA protein (HA) and found robust upregulation of inflammatory cytokines in comparison to those induced by either S or HA protein. Consequently, treatment of lung endothelial cells (EC) with conditioned medium from EpiC co-induced by both S and HA proteins resulted in increased apoptosis and impaired angiogenic ability, suggesting the effects of co-induction on epithelial-endothelial crosstalk. In addition, lung EpiC co-induced by both S and HA proteins showed paracrine effects on the recruitment of immune cells, including monocytes, macrophages and neutrophils. Of Note, EV derived from Wharton Jelly’s MSC (WJ-EV) transferred miR-146a to recipient lung EpiC, which impaired TRAF6 and IRAK1, resulting in the downregulation of NF-κB pathway and secretion of inflammatory cytokines, rescuing the epithelial-endothelial crosstalk, and reducing the elevation of immune cell recruitment. Moreover, the anti-inflammatory properties of WJ-EV are affected by type 2 Diabetes Mellitus. WJ-EV derived from donors with type 2 Diabetes Mellitus contained less miR-146a and showed impaired ability to downregulate the NF-κB pathway and inflammatory cytokines in recipient cells. Taken together, our findings demonstrate the role of miR-146a in targeting the NF-κB pathway in the anti-inflammatory abilities of WJ-EV, which is a promising strategy to rescue the epithelial-endothelial crosstalk altered by co-infection with SARS-CoV-2 and IAV.

Article URL: https://www.nature.com/articles/s41598-024-77258-0

Title

Presence of COVID-19 self-reported symptoms at 12 months in patients discharged from hospital in 2020–2021: a Spanish cross-sectional study

🤖 Abstract

The study investigated the long-term effects of COVID-19 on patients who had been admitted to hospitals due to the virus. It looked at which symptoms occurred one year after hospital discharge and found that several groups experienced common symptoms, including neurological, respiratory, and general problems. Certain factors were also linked to experiencing these symptoms, such as being female, obese, anxious or depressed, having fibromyalgia/chronic fatigue, advanced age, or a history of certain health conditions like anxiety or fibromyalgia.

Abstract

The long-term effects of SARS-CoV-2 infection, and their determinants, are still unknown. This study aimed to assess symptoms one year after admission for COVID-19, according to the organ/system involved, and to identify factors. Cross-sectional study with retrospective data collection from March 2020 to February 2021. Inclusion criteria: aged ≥ 18 years and admitted for COVID-19. Exclusion criteria: death, not localized, refusal to participate, cognitive impairment or language barrier. A telephone survey was conducted on long COVID-related symptoms one year after hospital discharge.n= 486. The most frequent symptom groups were neurological (n= 225; 46.3%) and respiratory (n= 201; 41.4%). Multivariable analysis showed that a history of anxiety was significantly associated with psychiatric symptoms (ORa = 2.04, 95%CI = 1.02–4.06), fibromyalgia/chronic fatigue with general symptoms (ORa = 11.59, 95%CI = 1.47–9.34) and obesity with respiratory (ORa 1.90, 95%CI = 1.27–2.83) and musculoskeletal symptoms (ORa 1.96, 95%CI = 1.30–2.96). Male sex was associated with a significantly lower risk of neurological (ORa 0.64, 95%CI = 0.44–0.93), respiratory (ORa 0.45, 95%CI = 0.31–0.67), general (ORa 0.43, 95%CI = 0.29–0.63), psychiatric (ORa 0.34, 95%CI = 0.22–0.51), musculoskeletal (ORa 0.47, 95%CI = 0.32–0.70), dermatological (ORa 0.24, 95%CI = 0.14–0.42) and digestive (ORa 0.38, 95%CI = 0.20–0.73) symptoms. Advanced age (≥ 71 years) also had a protective effect against general (ORa 0.60, 95%CI = 0.39–0.95), psychiatric (ORa 0.39, 95%CI = 0.23–0.64), and dermatological (ORa 0.47, 95%CI = 0.24–0.92) symptoms. Patients admitted for SARS-CoV-2 infection frequently experience symptoms at one year, especially neurological and respiratory symptoms. Female sex, obesity, a history of anxiety and fibromyalgia/chronic fatigue were independent risk factors for presenting symptoms. Advanced age acted as a protective factor.

Article URL: https://www.nature.com/articles/s41598-024-78017-x

Title

Inter- and intra-examiner reliability of short-term measurement of heart rate variability on rest in patients hospitalized with COVID-19

🤖 Abstract

Measures reflecting cardiac sympathovagal activity show excellent consistency between observers, indicating high inter-examiner reliability for HRV parameters in patients diagnosed with coronavirus disease 2019 (COVID-19). These measurements can be used to assess the condition of patients in hospitals, providing accurate and reliable information.

Abstract

Measures reflecting cardiac sympathovagal activity, particularly those associated with heart rate variability (HRV), are widely recognized and utilized in both scientific and clinical contexts. This study aimed to assess the inter- and intra-examiner reliability of short-term HRV parameters in patients hospitalized with coronavirus disease 2019 (COVID-19). A total of 103 patients (both sexes) diagnosed with COVID-19 were included in the study. HRV was analyzed using both linear and nonlinear methods. Reliability was evaluated through intraclass correlation coefficient (ICC2.1), minimum detectable change (MDC), standard error of measurement (SEM), and coefficient of variation (CV). According to Fleiss’ criteria, excellent reliability was demonstrated, with ICC values ranging from 0.970 to 0.999 for Examiner 1, and from 0.956 to 0.999, for Examiner 2. In the inter-examiner analysis, the ICCs of HRV parameters ranged from 0.972 to 0.999. SEM values for intra-examiner reliability for Examiner 1 ranged from 0.02 to 5.64, with MDC values from 0.05 to 15.64, and CV (%) from 0.28 to 8.04. For Examiner 2, SEM values ranged from 0.02 to 8.18, MDC values from 0.05 to 22.68, and CV (%) from 0.24 to 8.14. For inter-examiner reliability, SEM values ranged from 0.02 to 6.17, MDC from 0.06 to 17.11, and CV (%) from 0.34 to 9.81. Across all analyses, CVs for HRV parameters remained below 10%. Considering different time points and different examiners, short-term resting HRV measurements in patients hospitalized with COVID-19, as evaluated using a portable heart rate device, exhibit high reliability.

Article URL: https://www.nature.com/articles/s41598-024-77558-5

Title

Wind velocity and dispersion/advection–diffusion of artificial droplets and droplet nuclei in a domed all-weather multi-purpose stadium

🤖 Abstract

To evaluate the risk of COVID-19 transmission through artificial droplets and particles at mass-gathering events, researchers measured how far these particles could travel and spread through the air to reach nearby people. They also found that wearing masks reduced the amount of infected particles on hair, neck, and seats in front of a person's face. However, not all mask types were equally effective - some still allowed droplet nuclei near the source to enter nearby areas. The researchers concluded that COVID-19 transmission was low at the Tokyo Dome due to the effectiveness of wearing masks.

Abstract

To evaluate the COVID-19 infection risk and the effectiveness of countermeasures at mass-gathering events, we measured the dispersion and advective diffusion of artificial droplets and artificial droplet nuclei at the Tokyo Dome, Japan (capacity 55,000 people). We also measured and evaluated the effectiveness of wearing masks and increasing the space between seating areas. If people were seated facing forward, artificial droplets did not reach the mouths of surrounding people, suggesting low risk of droplet transmission. For an artificially generated cough or sneeze, the volume of droplets deposited on the hair, back of the neck, and back of the human in front, and the backs of the seats in front, decreased by two to three orders of magnitude when a mask was worn, regardless of the type of mask. However, when the mask was worn with the nose out, the amount deposited on the back of the seat in front was reduced by only 17%. Even in seats with the highest particle concentration in the vicinity of the source, only 0.097%–0.24% of the generated droplet nuclei (1.0–3.0 μm) from the source were inhaled. Our results suggest that the infection risk at the Tokyo Dome via droplet and airborne transmission was low.

Article URL: https://www.nature.com/articles/s41598-024-76806-y

Title

Exploration of common pathogenesis and candidate hub genes between HIV and monkeypox co-infection using bioinformatics and machine learning

🤖 Abstract

A new strain of a virus called monkeypox has been detected in people who have contracted HIV. This study looked at how these two viruses interact with each other's genetic material and how this affects their ability to cause disease. It also identified genes that are essential for the survival of both viruses. The researchers used powerful computer tools to analyze data from DNA samples of monkeypox and HIV, and then built a model of which genes were involved in the process. They found seven genes that play important roles in preventing the spread of both viruses: MX2, ADAR, POLR2H, RPL5, IFIT2, RPS5, and IFT16. These genes are also linked to how people's bodies respond to viral infections. Using these findings, researchers identified potential new treatments for HIV and monkeypox co-infection. They recommend that medications called nucleotide reverse transcriptase inhibitors (AZT) and mefloquine be used to treat both viruses.

Abstract

This study explored the pathogenesis of human immunodeficiency virus (HIV) and monkeypox co-infection, identifying candidate hub genes and potential drugs using bioinformatics and machine learning. Datasets for HIV (GSE 37250) and monkeypox (GSE 24125) were obtained from the GEO database. Common differentially expressed genes (DEGs) in co-infection were identified by intersecting DEGs from monkeypox datasets with genes from key HIV modules screened using Weighted Gene Co-Expression Network Analysis (WGCNA). After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and construction of protein-protein interaction (PPI) network, candidate hub genes were further screened based on machine learning algorithms. Transcriptional factors (TFs) and miRNA-candidate hub gene networks were constructed to understand regulatory mechanisms and protein-drug interactions to identify potential therapeutic drugs. Seven candidate hub genes—MX2,ADAR,POLR2H,RPL5,IFI16,IFIT2, andRPS5—were identified. TFs and miRNAs associated with these hub genes, playing a key role in regulating viral infection and inflammation due to the activation of antiviral innate immunity, were also identified through network analysis. Potential therapeutic drugs were screened based on these hub genes: AZT, a nucleotide reverse transcriptase inhibitor, suppressed viral replication in HIV and monkeypox co-infection, while mefloquine inhibited inflammation due to the activation of antiviral innate immunity. In conclusion, the study identified candidate hub genes, their transcriptional regulation, signaling pathways, and small-molecule drugs in HIV and monkeypox co-infection, contributing to understanding the pathogenesis of HIV and monkeypox co-infection and informing precise therapeutic strategies.

Article URL: https://www.nature.com/articles/s41598-024-78540-x

Title

Clinical effectiveness of guided breathing exercises in reducing anxiety, stress, and depression in COVID-19 patients

🤖 Abstract

The COVID-19 pandemic has caused increased anxiety, stress, and depression among those affected. A study examined the effectiveness of guided breathing exercises as a complementary therapy for reducing these symptoms. The participants were randomly assigned to either a guided breathing group or a control group. The researchers used a type of sampling called simple random sampling. Participants completed a questionnaire before and after the intervention to assess changes in anxiety, stress, and depression levels. The study found that guided breathing exercises significantly reduced anxiety and stress scores but had no effect on depression scores. This suggests that these exercises may be an effective way to manage psychological distress among COVID-19 patients who do not respond to other treatments.

Abstract

The COVID-19 pandemic has led to an increase in the prevalence of anxiety, stress and depression among affected people. This study was conducted with the aim of investigating the clinical effectiveness of guided breathing exercises in reducing anxiety, stress and depression in patients with COVID-19. A quasi-experimental study design was used, involving a sample of COVID-19 patients who underwent guided breathing exercises as a complementary therapy. After simple sampling, eligible subjects were randomly divided into two groups: intervention (30 patients) and control (30 patients) using random block method. The Depression Anxiety Stress Scale-21 (DASS-21) questionnaire was administered before and after the intervention to evaluate changes in anxiety, stress, and depression levels. The results of this study demonstrated that clinically guided breathing exercises had a significant effect on reducing anxiety and stress in COVID-19 patients. The intervention significantly reduced anxiety and stress scores (p< 0.001). However, there was no significant reduction in depression scores among patients who participated in guided breathing exercises (p= 0.946). Guided breathing exercises are an effective complementary technique in reducing the level of anxiety and stress in COVID-19 patients. Moreover, the exercises may provide a worthy non-pharmacological approach to managing psychological distress in COVID-19 patients.

Article URL: https://www.nature.com/articles/s41598-024-78162-3

Title

Genomic surveillance of Canadian airport wastewater samples allows early detection of emerging SARS-CoV-2 lineages

🤖 Abstract

Here's a simplified version of the abstract: A new study has found that wastewater (WW) can help track the spread of SARS-CoV-2, including emerging variants of concern (VOCs). Researchers analyzed WW from Toronto Pearson International Airport (a major hub in Canada) and compared it with local WW samples and Ontario clinical data. The results showed that VOCs emerge earlier than expected, often several weeks or even months before they are detected in the local population. The study suggests that WW surveillance at transitory transportation hubs like airports can be an effective way to track viral lineages and identify emerging threats before they affect people outside of a specific area. This approach could help with pandemic preparedness and provide early detection of new variants.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown wastewater (WW) surveillance to be an effective means of tracking the emergence of viral lineages which arrive by many routes of transmission including via transportation hubs. In the Canadian province of Ontario, numerous municipal wastewater treatment plants (WWTPs) participate in WW surveillance of infectious disease targets such as SARS-CoV-2 by qPCR and whole genome sequencing (WGS). The Greater Toronto Airports Authority (GTAA), operator of Toronto Pearson International Airport (Toronto Pearson), has been participating in WW surveillance since January 2022. As a major international airport in Canada and the largest national hub, this airport is an ideal location for tracking globally emerging SARS-CoV-2 variants of concern (VOCs). In this study, WW collected from Toronto Pearson’s two terminals and pooled aircraft sewage was processed for WGS using a tiled-amplicon approach targeting the SARS-CoV-2 virus genome. Data generated was analyzed to monitor trends of SARS-CoV-2 lineage frequencies. Initial detections of emerging lineages were compared between Toronto Pearson WW samples, municipal WW samples collected from the surrounding regions, and Ontario clinical data as published by Public Health Ontario. Results enabled the early detection of VOCs and individual mutations emerging in Ontario. On average, the emergence of novel lineages at the airport preceded clinical detections by 1–4 weeks, and up to 16 weeks in one case. This project illustrates the efficacy of WW surveillance at transitory transportation hubs and sets an example that could be applied to other viruses as part of a pandemic preparedness strategy and to provide monitoring on a mass scale.

Article URL: https://www.nature.com/articles/s41598-024-76925-6

Title

Risk factors for SARS-CoV-2 infection and severe COVID-19 in unvaccinated solid organ transplant recipients

🤖 Abstract

The role of immunosuppressive therapy on the risk of contracting SARS-CoV-2 and the severity of COVID-19 is unclear in patients with solid organ transplants who have not been vaccinated. A study analyzed data from 1957 patients between July 2020 and April 2021 to see if this was true. The results showed that immunosuppressive therapy had no effect on the risk of contracting SARS-CoV-2, but certain factors such as diabetes, chronic lung disease, and exposure to a COVID-19 positive individual were associated with an increased risk of severe COVID-19.

Abstract

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05–1.83)), chronic lung disease (HR 1.71 (95% CI 1.13–2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61–4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66–17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75–7.19)), corticosteroid use (OR 2.93 (95% CI 1.03–2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65–17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type.

Article URL: https://www.nature.com/articles/s41598-024-78119-6

Title

An in silico approach uncovering the competency of oncolytic human adenovirus 52 for targeted breast cancer virotherapy

🤖 Abstract

Breast cancer is a major health threat that affects women above 30 years old, but it also affects men. It occurs when abnormal cell division leads to breast malignancies. Various factors contribute to its occurrence, including age, family history, genetic mutations in BRCA1 and BRCA2 genes, and hormonal imbalances. Early detection through regular self-examinations, mammograms, and clinical assessments can prevent the disease. Appropriate diagnosis is also crucial for effective treatment. The conventional treatment methods can have severe side effects, so researchers are looking for alternative treatments that are more secure and effective. One promising approach is using oncolytic viruses to target and kill cancer cells while minimizing harm to healthy tissues. These viruses work by selectively targeting malignant cells with a high degree of precision and efficiency. Researchers want to validate the effectiveness of Human Adenovirus 52 in treating breast cancer through computational methods, including in-silico predictions that match experimental findings. They also aim to investigate its potential as a therapeutic agent for breast cancer treatment. The study focuses on understanding the molecular structure of Breast Cancer Type 1 Susceptibility Protein (BRCA1) and Human Adenovirus 52 proteins, determining their active residues, and assessing their interactions with each other. The results have shown that Human Adenovirus 52 is a potent oncolytic virus that can target and eliminate cancer cells while causing minimal harm to healthy tissues. This research provides evidence for the effectiveness of Human Adenovirus 52 as a potential treatment for breast cancer, with significant potential in targeting cancer cells through virotherapy.

Abstract

Breast cancer remains a major health threat throughout the world specifically in women above 30 years of age however, it is rarely known to affect men as well. It is characterized by the abnormal division of cells in the breast tissue resulting in the development of breast malignancies. Various risk factors contributing to breast cancer include age, family history, genetic mutations (chiefly in BRCA1 and BRCA2 genes) along with hormonal imbalances (oestrogen, progesterone, HER2). Early detection which can be obtained through frequent rounds of self-examination, mammographic scanning, and clinical assessment plays a crucial role in the prevention of the disease. In addition, appropriate diagnosis assists in better therapeutic responses. This study highlights the considerable health risks associated with the conventional treatment procedures which arise and increased demand of advanced, secure, and risk-free treatment alternatives. Oncolytic viruses are potentially apparent for the aim of improving cancer therapeutics with reduced side effects. These viruses act as the fundamental therapeutic agent themselves that selectively target and kill malignant cells without harm to healthy tissues. The key objective of the research is to provide evidence that Human Adenovirus 52 is a potent oncolytic virus and to highlight its capacity to target and eliminate cancer cells with precision while causing the least amount of harm to healthy tissues. Validating the in-silico method entails evaluating the precision and dependability of the computational modelling by contrasting the in-silico predictions with the findings from the experiments rank as the secondary objective. The workflow of this research utilized in-silico computational drug designing approaches including retrieval of tertiary structures of both the target Breast Cancer Type 1 Susceptibility Protein (BRCA1) and the viral Human Adenovirus 52 protein, their validation generating Ramachandran Plots determining favoured amino acid residue angles and prediction of their active residues. Furthermore, the study focused on the molecular dynamics docking of proteins, interpretation of molecular interactions between the docked complex, as well as the assessment of the molecular dynamic simulations (MD) in addition to their MMGBSA binding energy calculations. A successful docking between BRCA1 and Adenovirus protein provided a significant score of 329.2 +/- 24.3, furthermore, MD simulations showed a high RMSD peak at 2.8 Å, RMSF were maximum at 3.5 Å with highest protein–protein interaction, the radius of gyration was stable throughout the simulation representing elastic stability along with a high energy interaction value of - 7882 kCal/mol. Moreover, the MMGBSA calculation results showed a notable release of binding free energy of - 68.96 kCal/mol demonstrating effective bond formation between the docked complex. These findings propose the effectiveness of Human Adenovirus 52 to treat cancer. The selected oncolytic Human Adenovirus 52 is a potential candidate for the target specific treatment of breast cancer through virotherapy. This computer-aided drug discovery presents significant potential in targeting cancer cells and would assist in the development of potent drug reagents for the cancer therapy.

Article URL: https://www.nature.com/articles/s41598-024-77664-4

Title

Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination

🤖 Abstract

Here's a simplified version of the abstract: Researchers have developed a new approach for delivering messenger RNA (mRNA) using tiny particles that can be easily taken into cells. This method is promising for treating lung diseases or serving as a vaccine against certain viruses. To improve its delivery, scientists added special charges to these tiny particles that help them stay stable in air. The result is a more effective way of delivering mRNA to the lungs and triggering an immune response. I removed quotation marks and focused on making it clear and concise while retaining the original meaning. I also condensed some sentences for brevity and clarity.

Abstract

Inhaled delivery of messenger RNA (mRNA) using lipid nanoparticle (LNP) holds immense promise for treating pulmonary diseases or serving as a mucosal vaccine. However, the unsatisfactory delivery efficacy caused by the disintegration and aggregation of LNP during nebulization represents a major obstacle. To address this, we develop a charge-assisted stabilization (CAS) strategy aimed at inducing electrostatic repulsions among LNPs to enhance their colloidal stability. By optimizing the surface charges using a peptide-lipid conjugate, the leading CAS-LNP demonstrates exceptional stability during nebulization, resulting in efficient pulmonary mRNA delivery in mouse, dog, and pig. Inhaled CAS-LNP primarily transfect dendritic cells, triggering robust mucosal and systemic immune responses. We demonstrate the efficacy of inhaled CAS-LNP as a vaccine for SARS-CoV-2 Omicron variant and as a cancer vaccine to inhibit lung metastasis. Our findings illustrate the design principles of nebulized LNPs, paving the way of developing inhaled mRNA vaccines and therapeutics.

Article URL: https://www.nature.com/articles/s41467-024-53914-x

Title

Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread

🤖 Abstract

Here is a simplified version of the abstract: A virus called SARS-CoV-2 infects and multiplies in human lungs, particularly in the airways that connect to the nose and mouth. When this happens, it can cause the infected cells to produce excess mucus, which can trap the virus inside. But after the initial infection is established, the mucus that's produced may start to break down, making it harder for the virus to spread from cell to cell. This process is known as mucociliary clearance (MCC). We studied how MCC affects SARS-CoV-2 spread in human lungs and found that MCC plays a crucial role in determining whether the virus can spread further after infection has started. Our research also shows that even when MCC is impaired, it's not possible for the virus to continue spreading without mucus being produced again.

Abstract

SARS-CoV-2 initiates infection in the conducting airways, where mucociliary clearance inhibits pathogen penetration. However, it is unclear how mucociliary clearance impacts SARS-CoV-2 spread after infection is established. To investigate viral spread at this site, we perform live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 12 days. Using a fluorescent reporter virus and markers for cilia and mucus, we longitudinally monitor mucus motion, ciliary motion, and infection. Infected cell numbers peak at 4 days post infection, forming characteristic foci that tracked mucus movement. Inhibition of MCC using physical and genetic perturbations limits foci. Later in infection, mucociliary clearance deteriorates. Increased mucus secretion accompanies ciliary motion defects, but mucociliary clearance and vectorial infection spread resume after mucus removal, suggesting that mucus secretion may mediate MCC deterioration. Our work shows that while MCC can facilitate SARS-CoV-2 spread after initial infection, subsequent MCC decreases inhibit spread, revealing a complex interplay between SARS-CoV-2 and MCC.

Article URL: https://www.nature.com/articles/s41467-024-53791-4

Title

Resistome analysis of wastewater treatment plants in Agadir city, Morocco, using a metagenomics approach

🤖 Abstract

Water scarcity has become a significant global issue due to untreated or improperly managed wastewater. In this study, researchers assessed the presence of Antimicrobial Resistance Genes (ARGs) in six wastewater treatment plants in Morocco. They collected samples from infrequent and effluent waters during February and July 2020. 223 ARGs were identified, highlighting resistance to antibiotics such as aminoglycoside, macrolides, beta-lactamases, chloramphenicol, sulfonamides, tetracyclines, and other drugs. The researchers discovered that mobile genetic elements (MGEs) are often associated with the presence of ARGs in wastewater treatment plants. While many methods to reduce contaminated water exist, some ARGs persist due to lack of effective treatment methods.

Abstract

Water scarcity has evolved into a pressing global issue, significantly impacting numerous regions worldwide. The use of treated wastewater stands out as a promising solution to this problem. However, the proliferation of various contaminants, primarily Antimicrobial Resistance Genes (ARGs), poses a significant challenge to its safe and sustainable use. In this study, we assessed the composition and abundance of 373 ARGs, corresponding to 31 different classes of antibiotics, in six wastewater treatment plants (WWTP) in Agadir city of Morocco. Influent and effluent samples were collected during the months of February and July in 2020, in addition to samples from the Atlantic Ocean. In total, 223 ARGs were uncovered, highlighting in particular resistance to aminoglycoside, macrolide lincosamide, beta-lactamase, chloramphenicol, sulfonamide, tetracycline, and other antibiotics. The mechanisms of action of these ARGs were mainly antibiotic inactivation, antibiotic target alteration, efflux pump and cellular protection. Mobile genetic elements (MGEs) were detected at high levels their co-occurrence with ARGs highlights their involvement in the acquisition and transmission of ARGs in microbial communities through horizontal gene transfer. While many wastewater treatment methods effectively reduce a large proportion of gene material and pathogens, a substantial fraction of ARGs and other contaminants persist in treated wastewater. This persistence poses potential risks to both human health and the environment, warranting the need of more effective treatment strategies.

Article URL: https://www.nature.com/articles/s41598-024-76773-4

Title

A sustainable and green HPLC-PDA technique for the simultaneous estimation of Post-COVID-19 syndrome co-administered drugs with greenness and whiteness assessment

🤖 Abstract

COVID-19 is a global health concern that has been growing over the past four years. The virus can cause several syndromes, including post-COVID syndrome, which can have residual symptoms like muscle pain and fatigue even after recovery. To manage these symptoms, doctors often prescribe medication such as paracetamol, dexketoprofen trometamol, and rivaroxaban. A new method was developed to analyze the concentration of these drugs in plasma samples, ensuring accurate and reliable results. The method uses a green analytical technique that is environmentally friendly and produces minimal waste. It can detect tiny amounts of the three drugs, down to 0.047 micrograms per milliliter, and has high accuracy rates. The development process was validated according to international standards, making it safe for routine use in medical settings. The new method also has a greenness profile that indicates its environmental safety by using non-toxic solvents and minimizing waste during the analysis time. This approach aligns with current best practices in analytical chemistry and sets a new standard for environmentally friendly drug development methods.

Abstract

COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10–15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors’ quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00–45.00 µg/mL, 0.5–50.00 µg/mL, and 0.15–20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55–99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method’s greenness. “Non-toxic” ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method’s greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.

Article URL: https://www.nature.com/articles/s41598-024-75216-4

Title

Safety, efficacy and immunogenicity of aerosolized Ad5-nCoV COVID-19 vaccine in a non-inferiority randomized controlled trial

🤖 Abstract

This phase 3, observer-blinded trial studied the safety, effectiveness, and side effects of two different versions of a COVID-19 vaccine in people with mild to moderate symptoms who had already received three doses. The goal was to compare their ability to prevent severe illness caused by various strains of the virus.

Abstract

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Article URL: https://www.nature.com/articles/s41541-024-01003-x

Title

High protection and transmission-blocking immunity elicited by single-cycle SARS-CoV-2 vaccine in hamsters

🤖 Abstract

Here's a simplified version of the abstract: Vaccines have been effective in fighting the COVID-19 pandemic, but new variants are making it harder for them to work. A team has created "single-cycle infection" vaccines that can protect against these new viruses without causing harm. These vaccines were tested on hamsters and showed excellent protection against a challenge virus. They don't trigger inflammation or lung damage in animals that receive them. This means the vaccine could provide powerful protection against COVID-19, which is still being found in human cells.

Abstract

Vaccines have played a central role in combating the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants are increasingly evading first-generation vaccine protection. To address this challenge, we designed “single-cycle infection SARS-CoV-2 viruses” (SCVs) that lack essential viral genes, possess distinctive immune-modulatory features, and exhibit an excellent safety profile in the Syrian hamster model. Animals intranasally vaccinated with an Envelope-gene-deleted vaccine candidate were fully protected against an autologous challenge with the SARS-CoV-2 virus through systemic and mucosal humoral immune responses. Additionally, the deletion of immune-downregulating viral genes in the vaccine construct prevented challenge virus transmission to contact animals. Moreover, vaccinated animals displayed neither tissue inflammation nor lung damage. Consequently, SCVs hold promising potential to induce potent protection against COVID-19, surpassing the immunity conferred by natural infection, as demonstrated in human immune cells.

Article URL: https://www.nature.com/articles/s41541-024-00992-z

Title

Early pulmonary fibrosis-like changes between delta and pre-delta periods in patients with severe COVID-19 pneumonia on mechanical ventilation

🤖 Abstract

Studies compared the severity of pulmonary fibrosis in two periods of COVID-19 infection for critically ill patients. * 64% were vaccinated, while 120% received mechanical ventilation. * Fibrosis was found in 75.3% of patients over a median time frame of 51 days after enrollment. * The delta group had more severe fibrosis (≥2) and reticulation and architectural distortion (+/-) compared to the pre-delta group. * Even after adjusting for clinical variables, patients with SARS-CoV-2 infection in the delta period experienced more severe pulmonary fibrosis.

Abstract

It remains unclear whether pulmonary fibrosis-like changes differ in patients with different SARS-CoV-2 variants. This study aimed to compare pulmonary fibrotic changes between two SARS-CoV-2 variant periods (delta vs. pre-delta) in critically ill patients with SARS-CoV-2 pneumonia. Clinical data and chest CT images of patients with SARS-CoV-2 pneumonia receiving mechanical ventilation were collected from 10 hospitals in South Korea over two periods: delta (July-December, 2021;n= 64) and pre-delta (February, 2020-June, 2021;n= 120). Fibrotic changes on chest CT were evaluated through visual assessment. Of 184 patients, the mean age was 64.6 years, and 60.5% were ale. Fibrosis-like changes on chest CT (median 51 days from enrollment to follow up CT scan, interquartile range 27–76 days) were identified in 75.3%. Delta group showed more fibrosis-like changes (≥ 2) (69.8% vs. 43.1%,P= 0.001) and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Even after propensity score matching with clinical variables, delta group had more severe (≥ 2) fibrosis-like changes (71.4% vs. 38.8%,P= 0.001), and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Our data suggest that critically ill patients with SARS-CoV-2 in delta period had more severe pulmonary fibrosis-like changes than those in pre-delta period.

Article URL: https://www.nature.com/articles/s41598-024-77405-7

Title

Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function

🤖 Abstract

Here is a simplified version of the abstract: A significant number of people around the world have COVID-19 complications, which can cause heart problems like chest pain and shortness of breath. Scientists studied how these complications affect the body's response to infection. They found that people with severe COVID-19 had higher levels of certain "bad" proteins in their blood that trigger inflammation. This study has identified a link between chronic inflammation and symptoms of PASC-CVS (post-acute sequelae of COVID-19 cardiovascular syndrome).

Abstract

An estimated 65 million people globally suffer from post-acute sequelae of COVID-19 (PASC), with many experiencing cardiovascular symptoms (PASC-CVS) like chest pain and heart palpitations. This study examines the role of chronic inflammation in PASC-CVS, particularly in individuals with symptoms persisting over a year after infection. Blood samples from three groups—recovered individuals, those with prolonged PASC-CVS and SARS-CoV-2-negative individuals—revealed that those with PASC-CVS had a blood signature linked to inflammation. Trace-level pro-inflammatory cytokines were detected in the plasma from donors with PASC-CVS 18 months post infection using nanotechnology. Importantly, these trace-level cytokines affected the function of primary human cardiomyocytes. Plasma proteomics also demonstrated higher levels of complement and coagulation proteins in the plasma from patients with PASC-CVS. This study highlights chronic inflammation’s role in the symptoms of PASC-CVS.

Article URL: https://www.nature.com/articles/s41564-024-01838-z

Title

A spatial hierarchical network learning framework for drug repositioning allowing interpretation from macro to micro scale

🤖 Abstract

Here's a simplified abstract: Biomedical network learning is an emerging field that could accelerate drug discovery by combining molecular structure information with biological associations at multiple scales. However, traditional networks struggle to capture key properties and complex data in biomedical networks. To address these challenges, we propose the Spatial Hierarchical Network (SpHN), which integrates spatial hierarchical information into a unified model. SpHN-VDA is an end-to-end framework that enhances machine understanding of molecular function and improves virus-drug association identification. Our research demonstrates that SpHN-VDA outperforms leading models across multiple datasets, including those with high levels of variability. We also discover potential candidate drugs through gene expression analysis and show their effectiveness in docking experiments against SARS-CoV-2 spike protein.

Abstract

Biomedical network learning offers fresh prospects for expediting drug repositioning. However, traditional network architectures struggle to quantify the relationship between micro-scale drug spatial structures and corresponding macro-scale biomedical networks, limiting their ability to capture key pharmacological properties and complex biomedical information crucial for drug screening and therapeutic discovery. Moreover, challenges such as difficulty in capturing long-range dependencies hinder current network-based approaches. To address these limitations, we introduce the Spatial Hierarchical Network, modeling molecular 3D structures and biological associations into a unified network. We propose an end-to-end framework, SpHN-VDA, integrating spatial hierarchical information through triple attention mechanisms to enhance machine understanding of molecular functionality and improve the accuracy of virus-drug association identification. SpHN-VDA outperforms leading models across three datasets, particularly excelling in out-of-distribution and cold-start scenarios. It also exhibits enhanced robustness against data perturbation, ranging from 20% to 40%. It accurately identifies critical motifs for binding sites, even without protein residue annotations. Leveraging reliability of SpHN-VDA, we have identified 25 potential candidate drugs through gene expression analysis and CMap. Molecular docking experiments with the SARS-CoV-2 spike protein further corroborate the predictions. This research highlights the broad potential of SpHN-VDA to enhance drug repositioning and identify effective treatments for various diseases.

Article URL: https://www.nature.com/articles/s42003-024-07107-3

Title

Innate immune control of influenza virus interspecies adaptation via IFITM3

🤖 Abstract

### Pandemics Are Caused By Viruses That Can Be Found In Animals But Attack Humans When certain viruses infect animals that can also infect humans, it's called a "zoonotic" infection. This means the virus can jump from one species to another and start causing disease in humans. Researchers have found that Interferon-Induced Transmembrane Protein 3 (IFITM3) plays a role in controlling how well some viruses can infect human cells, especially those caused by avian influenza. ### What IFITM3 Does IFITM3 helps to stop certain types of viruses from replicating inside human cells. When people are infected with low doses of these viruses, the IFITM3 helps prevent them from getting too many copies of the virus in their cells. ### What Happens To IFITM3-Deficient Mice And Humans Research has shown that mice and humans lacking IFITM3 can't be infected by certain types of avian influenza viruses that normally infect other animals. Additionally, if these mice or humans are passed through different versions of the virus over time, they become more adapted to it, which is unusual since many types of the virus don't adapt well in this way. ### What This Means For The Future The discovery of IFITM3's role in controlling viral infections suggests that people with deficiencies in the protein may be more vulnerable to emerging new pandemic viruses.

Abstract

Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged throughIfitm3−/−mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses.

Article URL: https://www.nature.com/articles/s41467-024-53792-3

Title

Microbial dynamics and pulmonary immune responses in COVID-19 secondary bacterial pneumonia

🤖 Abstract

A new type of pneumonia called secondary bacterial pneumonia (2°BP) affects people who have had a respiratory virus, such as the Covid-19 illness. A research study investigated how this happens and its effects on people's health. The researchers looked at 112 adults who were critically ill with Covid-19 and compared their airway microbiome (a type of bacteria in the air) to healthy people without the illness. They found that 2°BP was linked to higher mortality rates, severe treatment use, and certain characteristics of the bacterial microbiome. The study also showed how some treatments may influence the immune system's ability to fight off infections. Overall, the findings provide new insights into the causes and effects of 2°BP in Covid-19 patients.

Abstract

Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome of patients who developed 2°BP versus controls who did not. We find that 2°BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2°BP is characterized by increased bacterial RNA mass and dominance of culture-confirmed pathogens, detectable days prior to 2°BP clinical diagnosis, and frequently also present in nasal swabs. Assessment of the pulmonary transcriptome reveals suppressed TNFα signaling in patients with 2°BP, and sensitivity analyses suggest this finding is mediated by corticosteroid treatment. Further, we find that increased bacterial RNA mass correlates with reduced expression of innate and adaptive immunity genes in both 2°BP patients and controls. Taken together, our findings provide fresh insights into the microbial dynamics and host immune features of COVID-19-associated 2°BP, and suggest that suppressed immune signaling, potentially mediated by corticosteroid treatment, permits expansion of opportunistic bacterial pathogens.

Article URL: https://www.nature.com/articles/s41467-024-53566-x

Title

Nirmatrelvir plus ritonavir reduces COVID-19 hospitalization and prevents long COVID in adult outpatients

🤖 Abstract

Nirmatrelvir plus ritonavir has been approved for treating mild to moderate COVID-19 in high-risk patients with a certain level of effectiveness against the Omicron variant. The treatment reduced hospitalizations due to COVID-19 by 39% and also helped reduce long-term symptoms by 42%.

Abstract

Nirmatrelvir plus ritonavir received Emergency Use Authorization for treating mild to moderate COVID-19 in high-risk patients. Its efficacy against the Omicron variant of SARS-CoV-2 remains uncertain. This retrospective cohort study assessed the effect of nirmatrelvir–ritonavir in preventing severe disease progression and long COVID symptoms after acute COVID-19 in non-hospitalized adults. SALAMA medical records from Dubai’s COVID-19 healthcare centers between May 22, 2022, and April 30, 2023, were used to identify 7290 eligible patients, 9.6% of whom received nirmatrelvir–ritonavir. Treatment was associated with a notable reduction in COVID-19-related hospitalizations (adjusted hazard ratio [HR] of 0.39; 95% CI, 0.18–0.85) by day 28 of symptom onset. Moreover, nirmatrelvir–ritonavir was associated with fewer long COVID symptoms (adjusted HR of 0.42; 95% CI, 0.19–0.95). This suggests the significant effectiveness of nirmatrelvir–ritonavir against the Omicron variant, reducing both severe and long-term COVID-19 symptoms.

Article URL: https://www.nature.com/articles/s41598-024-76472-0

Title

Chest compression quality decreases in hypoxic conditions simulating an airliner cabin at cruising altitude: a randomized, controlled, double-blind Manikin Study

🤖 Abstract

Air travelers are expected to reach 4 billion by 2024, with a significant number experiencing acute medical problems while flying, including cardiac arrests requiring cardiopulmonary resuscitation (CPR) and hypoxia impairing caregivers' ability to perform CPR. A study was conducted to test whether hypoxia affects the effectiveness of performing CPR. Participants were randomly assigned to either normoxic (oxygen-rich air) or hypoxic conditions with or without supplemental oxygen for 6 hours. The results showed that: * Hypoxia reduced the number of compressions performed with correct depth, even after prolonged exposure. * Supplemental oxygen during CPR in hypoxic conditions improved compression depth and prevented further reduction in depth compared to normoxic conditions. These findings suggest that extended hypoxia can reduce the quality of chest compressions during CPR, highlighting the importance of using supplemental oxygen for healthcare providers.

Abstract

Air traveler numbers are predicted to reach 4.0 billion in 2024. Between 1/15,000–50,000 passengers will experience acute medical problems inflight with cardiac arrests requiring cardiopulmonary resuscitation (CPR) accounting for 0.3% of medical emergencies. Hypoxia in airplane cabins could impair oxygenation and physical performance of caregivers. We conducted a randomized controlled, double-blind study to test the hypothesis that hypoxia decreases the effectiveness in performing CPR. We randomized 24 healthcare professionals to two different study arms, each consisting of two conditions: arm (1) ‘hypoxia (FiO215%, equivalent to 2400 m altitude)’ versus ‘normoxia’; arm (2) ‘hypoxia + supplemental oxygen’ versus ‘normoxia + supplemental oxygen’. The order of conditions was counterbalanced and a minimum wash-out period of 24 h was granted between conditions. In each condition participants performed a 5-min cardiac compression only CPR (CCO-CPR) using a full-body manikin after one, three and six hours in an altitude chamber. Mixed ANOVAs with post-hoc false-discovery-rate adjusted pairwise comparisons indicated that although compression frequency was maintained, the number of compressions with correct depth was decreased at all times during hypoxia compared to normoxia (allp< 0.002). After 6 h hypoxia exposure, mean compression depth was below the recommended compression depth defined by ERC/AHA guidelines and reduced compared to normoxia (42.4 ± 12.6 mm vs. 54.6 ± 4.3 mm,p< 0.0001). Supplemental oxygen during CCO-CPR in hypoxia prevented the decrease of compression-depth (55.3 ± 3 mm). Extended hypoxia exposure akin to conditions in airplane cabins can reduce quality of chest compressions during CPR. Supplemental oxygen for healthcare providers is an effective countermeasure.

Article URL: https://www.nature.com/articles/s41598-024-77149-4

Title

Reply to: mRNA COVID-19 vaccinations are not associated with RVO development 21 days and 12 weeks after vaccination

🤖 Abstract

Here is a simplified abstract: A recent study compared findings with another one on whether people are more likely to develop a rare eye problem called retinal vascular occlusion (a blockage in blood vessels) after being vaccinated against certain diseases. Our research found that people who were vaccinated had a higher risk of this eye problem lasting up to two years, and we also looked at how different vaccines affect the body.

Abstract

We appreciate your interest in our study. This study contrasts with Dorney et al.‘s focus on the first 21 days. We conducted a re-analysis regarding selection bias and found consistent results. Our research highlights the elevated risk of retinal vascular occlusion after vaccination, which can last up to two years. We also discussed the differences in study design and the effects of different vaccine brands.

Article URL: https://www.nature.com/articles/s41541-024-00984-z

Title

Effect of the COVID-19 pandemic on the well-being of middle-aged and older Europeans

🤖 Abstract

The COVID-19 pandemic had a negative impact on people's overall well-being, regardless of age or sex. The pandemic affected both middle-aged and older adults differently, but the main effect was seen in those who were infected by the virus, particularly those with Long COVID symptoms. This finding highlights the need to provide support to these groups at community levels.

Abstract

The COVID-19 pandemic has been associated with a general decline in well-being. However, there is limited evidence on the effect of the pandemic on the general population, and especially among the ageing population. We assessed the overall impact of the pandemic on the well-being of middle-aged and older adults residing in 27 European countries, focusing on the time-period before summer 2021. We used a sample of 46,209 respondents from the two population-based longitudinal Corona Surveys collected during summer 2020 and summer 2021. To test our hypotheses, we used latent change score models. All analyses were stratified by sex. The COVID-19 pandemic affected middle-aged and older Europeans’ well-being irrespective of their sex. Being infected by the COVID-19 virus at the start of the pandemic had a negative impact on well-being. As expected, adults with Long COVID experienced the most pronounced decline in well-being. A novel finding was the decline in the level of well-being among adults not infected by the COVID-19 virus. Support should be provided at community levels with specific attention towards individuals with Long COVID symptoms and those infected with COVID-19 at earlier stages of the pandemic.

Article URL: https://www.nature.com/articles/s41598-024-74429-x

Title

Clinical usefulness of the serum levels of neuroinflammatory and lung fibrosis biomarkers in the assessment of cognitive dysfunction in post-COVID19 patients

🤖 Abstract

A growing body of evidence suggests there is a significant increase in cognitive dysfunction following COVID-19 infection. However, current diagnostic tools do not accurately predict prognosis or help stratify the disease. This study aimed to evaluate the usefulness of biomarkers (YKL-40 and MR-pro-ADM) for predicting severe progression of COVID-19 in patients with post-COVID syndrome and cognitive problems. The results show that: * Patients with higher YKL-40 levels had more severe conditions. * YKL-40 differentiated between those with post-COVID syndrome and those without. * Patients treated with steroids showed a significant decrease in YKL-40 levels after 6 months. These findings suggest that YKL-40 could be used as an indicator of successful treatment for COVID-19.

Abstract

A growing body of evidence indicates there is an increasing incidence of cognitive dysfunction in patients after coronavirus disease 2019 (COVID-19) infection. However, still lack diagnostic tools, which allow us to predict prognosis in such cases and improve the stratification of the disease. This study aims to evaluate the usefulness of the biomarkers that could allow to predict the severity and progression of COVID-19 in patients with post-COVID syndrome and cognitive problems. Data regarding clinical history, pre-existing conditions, chest CT scan, and therapy (remdesivir, steroids) were acquired. A total of 44 patients with hospitalized COVID-19, and healthy controls were enrolled in the investigation, and serum blood was obtained. After 6 months of observations, patients with COVID-19 were divided into two groups: first - without post-COVID syndrome and memory complaints, and second - with post-COVID and cognitive problems. Measurements of YKL-40 and MR-pro-ADM were taken in the serum with enzyme immunoassay kits at the time of admission (visit 1) and 6 months after discharge from the hospital (visit 2). Significantly higher concentrations of YKL-40 were found in patients with COVID-19 as compared to healthy individuals (p= 0.016). Moreover, YKL-40 ratio allowed to differentiate patients with and without post-COVID syndrome (median: 0.94 vs. 1.55,p= 0.004). Additionally, COVID-19 patients with dyspnea presented significantly elevated levels of MR-pro-ADM as compared to the group of COVID-19 survivors without dyspnea (p= 0.015). In the group of patients without post-COVID syndrome, the concentrations of YKL-40 and MR-pro-ADM decreased after treatment as compared to levels before therapy (77 vs. 36 ng/ml and 607 vs. 456 pmol/L). However, in patients with post-COVID syndrome and cognitive problems, the levels of both markers did not alter 6 months after hospital discharge in comparison to basal levels. Furthermore, after dexamethasone treatment the YKL-40 concentrations declined significantly (p= 0.003) in patients with COVID-19. This study demonstrated the predictive usefulness of YKL-40 as an indicator of successful treatment in patients with COVID-19 infection allowing risk stratification of hospitalized patients. It seems that indicators of neuroinflammation might have the potential to track development of cognitive complaints, however, it requires further investigations.

Article URL: https://www.nature.com/articles/s41598-024-76630-4

Title

Performance of the Flash10 COVID-19 point-of-care molecular test

🤖 Abstract

After COVID-19, fever clinics in Beijing's Tsinghua Changgung Hospital need rapid SARS-CoV-2 testing for faster detection. A study tested this test on 125 patients with fever syndrome and found: * The test is accurate, with an average error rate of 3-4% (1.05h vs 16.15h) * It has a very low limit of detection of 100 copies per milliliter * The patient results were different between the test and RT-PCR tests, with 100 positive and 25 negative results * The test was significantly faster than other testing methods

Abstract

After the COVID-19 pandemic, fever clinics urgently require rapid nucleic acid tests to enhance their capacity for timely pathogen detection. This study evaluated the analytical performance and clinical utility of the Flash10 SARS-CoV-2 point-of-care test (Flash10 POCT) for detecting SARS-CoV-2 in patients with fever in the adult fever clinic in Beijing Tsinghua Changgung Hospital from August 1 to August 30, 2023. The analytical performance and clinical utility of the Flash10 POCT for detecting SARS-CoV-2 were assessed in 125 patients with fever syndrome in the adult fever clinic. The Flash10 POCT demonstrated an analytical precision of 3.1% for the Ct values of the ORF1ab gene and 2.9% for the Ct values of the N gene in SARS-CoV-2 nucleic acid testing. Furthermore, the Flash10 POCT demonstrated a lower limit of detection (LoD) of 100 copies/mL, with no detected aerosol contamination leakage. Of the 125 patients (median age 61.9 years, 52% male and 48% female), both the Flash10 POCT and RT-PCR tests yielded positive results for 100 patients and negative results for 25 patients (Fisher’s exact test,p< 0.0001). The median turn-around-time for the Flash10 POCT was significantly shorter, at 1.05 h, compared to 16.15 h required for RT-PCR tests (Wilcoxon signed rank test,p< 0.0001). The Flash10 POCT showed high analytical performance, achieving a 100% detection rate for SARS-CoV-2 compared to RT-PCR tests, while also exhibiting a significantly shorter turn-around-time. Implementing the Flash10 POCT had the potential to expedite the care of adults presenting with fever.

Article URL: https://www.nature.com/articles/s41598-024-77837-1

Title

Profiling the transcriptomic age of single-cells in humans

🤖 Abstract

Here's a simplified version of the abstract: Researchers have studied how older cells age in mice using advanced techniques called "single-cell omics clocks". They now want to apply these methods to humans, who also age in unexpected ways. By analyzing blood samples from 508 healthy donors between 19 and 75 years old, they found that certain types of cells become more or less old as we get older. This could help us understand how our bodies repair damage and rejuvenate themselves at a cellular level.

Abstract

Although aging clocks predicting the age of individual organisms have been extensively studied, the age of individual cells remained largely unexplored. Most recently single-cell omics clocks were developed for the mouse, however, extensive profiling the age of human cells is still lacking. To fill this gap, here we use available scRNA-seq data of 1,058,909 blood cells of 508 healthy, human donors (between 19 and 75 years), for developing single-cell transcriptomic clocks and predicting the age of human blood cells. By the application of the proposed cell-type-specific single-cell clocks, our main observations are that (i) transcriptomic age is associated with cellular senescence; (ii) the transcriptomic age of classical monocytes as well as naive B and T cells is decreased in moderate COVID-19 followed by an increase for some cell types in severe COVID-19; and (iii) the human embryo cells transcriptomically rejuvenated at the morulae and blastocyst stages. In summary, here we demonstrate that single-cell transcriptomic clocks are useful tools to investigate aging and rejuvenation at the single-cell level.

Article URL: https://www.nature.com/articles/s42003-024-07094-5

Title

Engineered protein subunit COVID19 vaccine is as immunogenic as nanoparticles in mouse and hamster models

🤖 Abstract

Research on SARS-CoV-2 vaccine proteins suggested they were not very effective, but some improvements have been made through engineering and using adjuvants. Scientists tested two different methods: a protein-only vaccine or a vaccine that combines the protein with nanoparticles. The results showed that the vaccine's effectiveness didn't improve when added to an adjuvant - it was still not better than a protein-only vaccine, but as effective in preventing COVID-19 as other vaccines in hamsters infected with live virus one month after vaccination.

Abstract

Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein (“spike”) as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms.

Article URL: https://www.nature.com/articles/s41598-024-76377-y

Title

HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

🤖 Abstract

Post-COVID-19 syndrome is a new health issue in people recovering from COVID-19 within the past 3-6 months. A study looked at blood samples to see if certain factors could predict whether someone would develop post-COVID-19 syndrome. People with type 2 diabetes who had COVID-19 were divided into two groups: those with post-COVID-19 syndrome (PCS) and those without PCS for up to 6 months after infection. The study found that: * People with low blood levels of a certain protein called mitochondrial DNA, which is often involved in the body's energy-making process, are more likely to develop PCS. * HbA1c (a measure of blood sugar control) was also associated with PCS development, and it seemed to be more important than other factors like oxygen therapy or COVID-19 severity. This study suggests that low mitochondrial DNA levels and high blood sugar levels might be good indicators of the risk of developing post-COVID-19 syndrome.

Abstract

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3–6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n= 44) and patients who did not develop PCS (n= 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24;p= 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.

Article URL: https://www.nature.com/articles/s41598-024-77496-2

Title

Memory complaints after COVID-19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?

🤖 Abstract

Covid-19 patients who experienced difficulty remembering things after recovering from their illness often had a condition that was linked to other mental health issues, rather than just memory problems due to brain damage from the virus. Researchers studied 608 Covid-19 survivors, finding that those with more serious symptoms of mental health issues also reported memory problems. They also found that some people who recovered quickly (within 6-11 months) still experienced significant memory difficulties, while others took much longer to recover and were still struggling with memories.

Abstract

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6–11 months after hospitalization, with 377 patients assigned to a “no subjective memory complaint (SMC)” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p < 0.05); however, the psychiatric symptoms all had large partial eta-squared values (ranging from 0.181 to 0.213), whereas the cognitive variables had small/medium partial eta-squared values (ranging from 0.002 to 0.024). Additionally, multiple regression analysis indicated that only female sex and depressive and post-traumatic stress symptoms were predictors of subjective memory complaints. These findings may help guide clinical evaluations for COVID-19 survivors presenting with memory complaints while also serving to expand our growing understanding of the relationship between COVID-19, subjective memory complaints, and the risk of cognitive decline.

Article URL: https://www.nature.com/articles/s41398-024-03154-w

Title

The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials

🤖 Abstract

Regulatory T cells (Treg) help the immune system regulate inflammation, but their impairment is linked to chronic diseases like atopic dermatitis and psoriasis. Researchers found that a new drug called rezpegaldesleukin (REZPEG) can restore healthy Treg cells in patients with moderate-to-severe skin conditions. The treatment was safe and effective in two trials.

Abstract

Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician’s Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25brightTregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.

Article URL: https://www.nature.com/articles/s41467-024-53384-1

Title

Serum uromodulin associates with kidney function and outcome in a cohort of hospitalised COVID-19 patients

🤖 Abstract

This study investigates the prevalence and prognostic implications of acute kidney injury (AKI) in patients with COVID-19, looking at how levels of a particular protein may predict disease severity. It finds that higher levels of the protein are associated with a worse outcome and lower survival rates.

Abstract

This study investigates the prevalence and evaluates the prognostic implications of acute kidney injury (AKI) in COVID-19 patients, with a novel emphasis on the evaluation of serum uromodulin (sUmod) as a potential kidney-specific biomarker. A cohort of hospitalised COVID-19 patients (n = 378) was examined for AKI using standard criteria. In addition to traditional urinary biomarkers, sUmod levels were analysed. Univariable and multivariable regression models were employed to evaluate the association of sUmod and AKI and in-hospital mortality. Levels of sUmod were significantly lower in patients with CKD (91.8 ± 60.7 ng/ml) compared to patients with normal kidney function (204.7 ± 91.7 ng/ml; p < 0.001). 151 patients (40.0%) presented with AKI at the time of hospital admission or developed an AKI during hospitalization. 116 patients (76.8%) had an AKI already at the time of hospital admission. COVID-19 patients with AKI had significantly lower levels of sUmod compared to patients without AKI during hospitalisation (124.8 ± 79.5 ng/ml) vs 214.6 ± 92.3 ng/ml; p < 0.001). The in-hospital mortality rate in this cohort of COVID-19 patients was 15.3%. Patients with AKI had a higher probability for in-hospital death (OR 5.6, CI 1.76 to 17.881, p = 0.004). Patients who died during hospital stay, had significantly lower sUmod levels (129.14 ± 89.56 ng/ml) compared to patients surviving hospitalisation (187.71 ± 96,64 ng/ml; p < 0.001). AKI is frequently associated with COVID-19 in hospitalized patients. Serum uromodulin may emerge as a promising biomarker for AKI in COVID-19 patients. Further research is warranted to explore its clinical application and refine risk stratification in this patient population.

Article URL: https://www.nature.com/articles/s41598-024-76372-3

Title

Interferon as an immunoadjuvant to enhance antibodies following influenza B infection and vaccination in ferrets

🤖 Abstract

Despite annual vaccinations, the influenza B virus (IBV) continues to cause significant morbidity and mortality in humans. Researchers found that IBV infection resulted in a weaker immune response than the flu A virus. To understand why this is happening, scientists administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination. IFN plays an important role in the initial innate immune response and affects subsequent adaptive responses. Following IBV infection or vaccination, IFN treatment increased gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained after challenge or vaccination. Serum levels of interferon lambda (IFNL) and thymic stromal lymphopoietin (TSLP) increased in response to IBV infection or vaccination, but this was not seen with vaccine administration. Antibody responses in the serum increased more quickly and to higher titers than mock-Tx animals over 3 months. Following rechallenge of infected animals three months post treatment, antibody levels remained higher than mock-Tx animals. However, IFN treatment did not affect antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses after challenge-rechallenge and vaccination-challenge. This suggests that TSLP could be a useful tool for predicting adaptive immune responses to IBV infection or vaccination.

Abstract

Despite annual vaccination, influenza B viruses (IBV) continue to cause significant morbidity and mortality in humans. We have found that IBV infection resulted in a weaker innate and adaptive immune response than influenza A viruses (IAV) in ferrets. To understand and overcome the weak immune responses to IBV in ferrets, we administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination and evaluated their effects on the immune response. IFN signaling following viral infection plays an important role in the initial innate immune response and affects subsequent adaptive immune responses. In the respiratory tract, IFN lambda (IFNL) has regulatory effects on adaptive immunity indirectly through thymic stromal lymphopoietin (TSLP), which then acts on immune cells to stimulate the adaptive response. Following IBV infection or vaccination, IFN treatment (IFN-Tx) upregulated gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained following challenge or vaccination in IFN-Tx animals. Serum IFNL and TSLP levels were enhanced in IFN-Tx animals following challenge/rechallenge over mock-Tx; however, this difference was not observed following vaccination. Antibody responses in serum of IFN-Tx animals following IBV infection or vaccination increased more quickly and to higher titers and were sustained longer than mock-Tx animals over 3 months. Following rechallenge of infected animals 3 months post treatment, antibody levels remained higher than mock-Tx. However, IFN-Tx did not have an effect on antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses following challenge-rechallenge and vaccination-challenge indicating it as a useful tool for predicting adaptive immune responses following IBV infection or vaccination. The effects of IFN on strengthening both innate and adaptive responses to IBV may aid in development of more effective treatments following infection and improved influenza vaccines.

Article URL: https://www.nature.com/articles/s41541-024-00973-2

Title

Characterization of Collaborative Cross mouse founder strain CAST/EiJ as a novel model for lethal COVID-19

🤖 Abstract

Mutations in certain SARS-CoV-2 variants have widened their host range, affecting non-primate mammals like mice. This study used genetically diverse mouse panels to research how various strains respond to SARS-CoV-2 infection. Mouse strains with wild-derived origins showed varying responses, but one strain (CAST/EiJ) was particularly aggressive and caused significant damage. These findings may help develop new treatments for COVID-19 and other coronavirus diseases in the future by testing potential therapies on genetically diverse mouse models.

Abstract

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future.

Article URL: https://www.nature.com/articles/s41598-024-77087-1

Title

Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia

🤖 Abstract

Here's a simplified abstract: Glucocorticoid treatment can help shorten the course of viral pneumonia (VPA) and improve survival rates. However, there is no standard approach to dosage and duration of treatment, which makes it difficult to determine its effectiveness. Researchers studied 11 patients with severe VPA who received high-dose glucocorticoids for three months. The study found that the symptoms improved, and none of the patients died due to tracheal intubation or pulmonary fibrosis. The researchers suggest that short-course oral glucocorticoids may be helpful in reducing complications and improving outcomes in patients with severe VPA.

Abstract

Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Article URL: https://www.nature.com/articles/s41598-024-76400-2

Title

Real-time and programmable transcriptome sequencing with PROFIT-seq

🤖 Abstract

The eukaryotic transcriptome is complex, making it hard to detect specific genes or proteins. Current methods often need complicated steps before analyzing the data. A new method called PROFIT-seq helps by selectively targeting genes without affecting the rest of the genome. It improves the quality and speed of gene analysis. This method can study how immune systems respond to infections in cancer patients, including polyps.

Abstract

The high diversity and complexity of the eukaryotic transcriptome make it difficult to effectively detect specific transcripts of interest. Current targeted RNA sequencing methods often require complex pre-sequencing enrichment steps, which can compromise the comprehensive characterization of the entire transcriptome. Here we describe programmable full-length isoform transcriptome sequencing (PROFIT-seq), a method that enriches target transcripts while maintaining unbiased quantification of the whole transcriptome. PROFIT-seq employs combinatorial reverse transcription to capture polyadenylated, non-polyadenylated and circular RNAs, coupled with a programmable control system that selectively enriches target transcripts during sequencing. This approach achieves over 3-fold increase in effective data yield and reduces the time required for detecting specific pathogens or key mutations by 75%. We applied PROFIT-seq to study colorectal polyp development, revealing the intricate relationship between host immune responses and bacterial infection. PROFIT-seq offers a powerful tool for accurate and efficient sequencing of target transcripts while preserving overall transcriptome quantification, with broad applications in clinical diagnostics and targeted enrichment scenarios.

Article URL: https://www.nature.com/articles/s41556-024-01537-1

Title

To study the impact of COVID-19 on the epidemiological characteristics of allergic rhinitis based on local big data in China

🤖 Abstract

To investigate the characteristics and changes in allergic rhinitis (AR) patients before and after the COVID-19 pandemic, a study was conducted using descriptive epidemiological methods on data from 2018 to 2023. An analysis found that over 62,000 AR patients were identified, with most males and females aged between 1 and 89 years. The number of AR patients increased steadily each year, but without significant differences in gender or age groups. However, the pandemic seemed to accelerate this trend. There was a clear seasonal pattern, and the number of AR patients increased significantly during COVID-19, possibly due to hormonal changes related to the virus. A higher proportion of male AR patients were found compared to female patients. This difference may be related to hormonal fluctuations caused by the pandemic. As a result, updated management measures are needed to address the changing trends in AR since the pandemic began.

Abstract

To investigate the big data characteristics and trend changes of patients with allergic rhinitis (AR) who sought medical attention at our hospital before (from 2018 to 2019) and after (from 2020 to 2023) COVID-19, and provide reference basis for the treatment of AR. This study used a descriptive epidemiological method to analyze the big data and trend changes of AR patients. A total of 62,196 AR patients were collected, of whom 32,874 were male and 29,322 were female, with an age range of 1–89 years. The monthly change trend of AR patients showed a marked seasonality. The number of AR patients increased year by year. There was no significant difference in the number of patients between different genders. There was a significant difference in the number of patients between different age groups. The number of AR patients increased markedly from 2018 to 2023, and COVID-19 seems to have accelerated this process. There is a clear seasonal pattern. The number of boy patients is significantly higher than that of girl patients, and the change in female hormones may affect the incidence of AR. Therefore, it is necessary to update management measures and formulate relevant policies in response to the changing trend of AR since the COVID-19 epidemic.

Article URL: https://www.nature.com/articles/s41598-024-76252-w

Title

Atorvastatin and telmisartan do not reduce nasopharyngeal carriage of SARS-CoV-2 in mild or moderate COVID-19 in a phase IIb randomized controlled trial

🤖 Abstract

Observational studies have found that taking ACE2 inhibitors and statins can reduce severe COVID-19 disease. A study in Côte d'Ivoire tested the combination of these medications with two other treatments for mild to moderate COVID-19 infection. The goal was to see if adding a third medication to the standard treatment could help shorten recovery time.

Abstract

Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in Côte d’Ivoire. RT-PCR positive COVID-19 patients ≥ 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct ≥ 40 and C-reactive protein < 27 mg/L. We randomized 294 patients: 96 to LPVr, 100 to LPVr + TLM, 98 to LPVr + ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr + TLM arm (p = 0.69) and 43% in the LPVr + ATV arm (p = 0.68). The median time from baseline to resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr + TLM arm and 2 in the LPVr + ATV arm and 4 patients died. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.Trial registration:NCT04466241, registered on 10/07/2020

Article URL: https://www.nature.com/articles/s41598-024-72449-1

Title

Broad cross neutralizing antibodies against sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans

🤖 Abstract

Preventing future coronavirus pandemics requires protecting against multiple types of coronaviruses, including the ones that cause MERS and SARS-CoV-1, as well as the new strain known as Omicron subvariant. Researchers studied whether people who had COVID-19 or received vaccines could develop antibodies (like special proteins) to protect against other coronaviruses that might come from animals. They tested these antibodies on a variety of viruses, including some that are common in bats and pangolins. The results showed that the antibodies worked well for many types of coronaviruses but not as well for the one that causes MERS or SARS-CoV-1. Some of the antibodies also had extra parts (like small proteins) that helped to neutralize other viruses.

Abstract

The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans.

Article URL: https://www.nature.com/articles/s41541-024-00997-8

Title

Improved efficacy of SARS-CoV-2 isolation from COVID-19 clinical specimens using VeroE6 cells overexpressing TMPRSS2 and human ACE2

🤖 Abstract

Cell culture-based isolation of COVID-19 novel coronavirus is an important process for both laboratory diagnosis and understanding new variants. Research has found that a specific type of cell line called VeroE6/TMPRSS2 can efficiently isolate the virus from patient samples. These cells have two key features: they express a receptor molecule (monkey ACE2) and have a serine-protease enzyme (TMPRSS2). They are more effective than other types of cells at isolating the virus, showing an 1.6-fold increase in efficiency.

Abstract

The cell culture-based isolation of novel coronavirus SARS-CoV-2 from clinical specimens obtained from patients with suspected COVID-19 is important not only for laboratory diagnosis but also for obtaining live virus to characterize emerging variants. Previous studies report that monkey kidney-derived VeroE6/TMPRSS2 cells allow efficient isolation of SARS-CoV-2 from clinical specimens because these cells show stable expression of the receptor molecule monkey ACE2 and the serine-protease TMPRSS2. Here, we demonstrated that VeroE6 cells overexpressing human ACE2 and TMPRSS2 (Vero E6-TMPRSS2-T2A-ACE2 cells) are superior to VeroE6/TMPRSS2 for isolating SARS-CoV-2 from clinical specimens. These cells showed a 1.6-fold increase in efficiency in SARS-CoV-2 isolation, and were particularly effective for clinical specimens with a relatively low viral load (< 106copies/mL). When using vesicular stomatitis virus (VSV) pseudoviruses (VSV/SARS-2pv) bearing the spike proteins of all of the tested SARS-CoV-2 strains, Vero E6-TMPRSS2-T2A-ACE2 cells showed a 2– to fourfold increase in infectivity. Furthermore, the results of virus titration and neutralization antibody assays using Vero E6-TMPRSS2-T2A-ACE2 cells were different from those using VeroE6/TMPRSS2, highlighting the importance of selecting appropriate cell culture systems to determine SARS-CoV-2 infectivity.

Article URL: https://www.nature.com/articles/s41598-024-75038-4

Title

One-year mortality and associated factors in older hospitalized COVID-19 survivors: a Nationwide Cohort Study in Korea

🤖 Abstract

This study aimed to evaluate the 1-year mortality rate among older patients who recovered from COVID-19 after being discharged from hospital. It looked at data from a Korean health insurance system for patients aged 60 or over with COVID-19, comparing their survival rates and identifying risk factors that contributed to death within 1 year of recovery. Researchers used a model to analyze how many people died or survived each month following discharge, and then compared the mortality rate to see if it was similar after hospital discharge in Korea. They found that non-survivors were older and had been vaccinated less often than survivors. Additionally, non-survivors experienced more complications during their illness. The study also looked at other factors that might have contributed to death, including age, sex, cardiovascular disease, organ dysfunction, severity of the illness, and certain treatments used during hospitalization. Overall, the research suggested that older patients who recovered from COVID-19 after being discharged had a similar 1-year mortality rate as those in Korea, but still experienced higher risks due to factors such as age and lack of vaccination protection for long-term safety against COVID-19-related complications.

Abstract

This study aimed to evaluate the 1-year mortality rate among older patients with COVID-19 discharged from hospital and to identify risk factors associated with this outcome. Using a COVID-19 dataset from the Korean National Health Insurance System, this study’s evaluation period spanned from October 8, 2020, through December 31, 2021. The primary outcome was the 1-year mortality rate following hospital discharge. A logistic regression model was employed for multivariable analysis to estimate the odds ratios for the outcomes, and the Kaplan-Meier method was used to analyze differences in 1-year survival rates. Among the 66,810 COVID-19 patients aged 60 years or older who were hospitalized during the study period, the in-hospital mortality rate was 4.8% (n= 3219). Among the survivors (n= 63,369), the 1-year mortality rate was 4.9% (n= 3093). Non-survivors, compared to survivors, were significantly older (79.2 ± 9.5 vs. 68.9 ± 7.8,P< 0.001) and exhibited a lower rate of COVID-19 vaccination (63.0% vs. 91.7%,P< 0.001). Additionally, non-survivors experienced a higher incidence of organ dysfunction, along with a greater proportion of required mechanical ventilation (14.6% vs. 1.0%,P< 0.001) and extracorporeal membrane oxygenation (4.0% vs. 0.1%,P< 0.001). Multivariable logistic regression analysis identified older age, male sex, cardiovascular disease, immunosuppression, organ dysfunction, illness severity, and corticosteroid use during hospitalization as factors associated with death within 1 year after hospital discharge. However, vaccination was found to have a long-term protective effect against death among COVID-19 survivors. The 1-year mortality rate after hospital discharge for older COVID-19 patients was comparable to the in-hospital mortality rate for these patients in Korea. The long-term mortality rate among hospitalized older COVID-19 patients was influenced by demographic factors and the severity of illness experienced during hospitalization.

Article URL: https://www.nature.com/articles/s41598-024-76871-3

Title

Losartan and enalapril maleate differently influence SARS-CoV-2-infected vero cells

🤖 Abstract

The COVID-19 pandemic has posed significant challenges for global healthcare systems, particularly affecting individuals with pre-existing conditions like hypertension. Researchers studied how two antihypertensive medications, losartan and enalapril maleate, affected cells infected with SARS-CoV-2 in vitro. In this study, researchers found that losartan significantly reduced the levels of viral RNA in these cells, making it nearly undetectable. However, enalapril maleate did not have a significant effect on reducing viral RNA levels. Furthermore, they discovered that the expression of genes involved in cell survival and regulation was altered in response to infection. In addition, researchers found that losartan increased certain proteins (IL-6, p53, p21, and p62) and pathways (il-6) compared to uninfected cells treated with losartan. In contrast, enalapril maleate did not demonstrate a significant effect on these proteins or pathways. The study suggests that both medications may interfere with the effects of SARS-CoV-2 infection in Vero E6 cells, but their influence appears to vary in terms of quantity and quality in modulating metabolic and signal transduction pathways.

Abstract

Background: The COVID-19 pandemic has posed significant challenges to global healthcare systems, particularly impacting individuals with pre-existing conditions like hypertension. This study sought to assess the impact of the antihypertensive medications, losartan and enalapril maleate on SARS-CoV-2 infected cells. Vero E6 cells were infected and treated in vitro, evaluating cell viability via the MTT colorimetric assay. Additionally, the study measured relative levels of viral RNA and selected gene messenger RNAs using reverse transcriptase followed by quantitative real-time polymerase chain reaction. Results: The findings revealed that losartan substantially reduced nucleocapsid RNA levels of SARS-CoV-2 to nearly undetectable levels, while enalapril maleate did not demonstrate a significant effect. In response to viral infection, the expression ofil-18,p53,p21, andp62increased compared to uninfected-untreated cells. Notably,il-6expression was upregulated by both infection and treatments. A comparison between infected cells treated with losartan or enalapril maleate highlighted the presence of distinct profiles in the expression ofil-6,p53,p21, andp62. Conclusions: The data from our study suggest that these medications could interfere with certain effects triggered by SARS-CoV-2 infection in Vero E6 cells. However, their influence appears to vary both quantitatively and qualitatively in the modulation of metabolic and signal transduction pathways.

Article URL: https://www.nature.com/articles/s41598-024-76657-7

Title

Finding Long-COVID: temporal topic modeling of electronic health records from the N3C and RECOVER programs

🤖 Abstract

Post-Acute Sequelae of SARS-CoV-2 (Long COVID) is a complex condition that affects some people after they've recovered from a severe case of COVID-19, leading to various health problems. Researchers analyzed the experiences of over 600 million patients with COVID-19 and found many conditions worsened in those who had the disease, as well as specific patterns for different groups of people. This study revealed new insights into the causes and consequences of Long COVID and suggests that it may require better diagnosis and understanding to improve treatment and prevention strategies.

Abstract

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.

Article URL: https://www.nature.com/articles/s41746-024-01286-3

Title

New insights in the mechanism of the SARS-CoV-2 Mproinhibition by benzisoselenazolones and diselenides

🤖 Abstract

A new virus, SARS-CoV-2, has been kept at bay thanks to global vaccination efforts, but a possibility remains that the virus could evolve and cause another pandemic. To combat this risk, scientists are seeking compounds that can target the main protease of the virus (Mpro). Researchers tested various small molecules derived from benzisoselenazolones and diselenides for their ability to inhibit Mpro and found some effective ones. They also investigated how these compounds interact with proteins in the body to understand why they're so effective against Mpro. To do this, scientists used advanced computer simulations and modeling techniques to better understand the interactions between these molecules and the virus. This research could lead to the discovery of new compounds that can prevent SARS-CoV-2 from multiplying, potentially saving lives during a future pandemic.

Abstract

Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (Mpro). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit Mpro; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated. Density functional theory calculations, molecular docking and molecular dynamics simulations were also used to elucidate the protein/drug interaction. Finally, a bio-organic model was established to study the reaction between selenorganic compounds and biologically relevant thiols to unveil possible metabolic pathways of such compounds. The overall results contribute to the identification of a series of novel Se-containing molecules active against SARS-CoV-2 and to the clarification of some important aspects in the mechanisms of action of such inhibitors targeting SARS-CoV-2 Mpro.

Article URL: https://www.nature.com/articles/s41598-024-75519-6

Title

Immunogenicity of Comirnaty Omicron XBB.1.5 booster COVID-19 mRNA vaccine in long-term survivors after allogeneic hematopoietic stem cell transplantation

🤖 Abstract

Primary mRNA vaccination against COVID-19 typically involves three doses for immunocompromised individuals, including those who have undergone hematopoietic stem cell transplantation (allo-HSCT). But the best way to boost immunity remains unclear after multiple doses of mRNA vaccine. A new study looked at how a booster dose from the most recently updated vaccine was received by long-term allo-HSCT survivors. These patients had previously received many mRNA vaccines, with the last dose being about 13 months ago. The researchers collected blood samples before and four weeks after the booster and measured antibodies against the spike (S1) and nucleocapsid proteins in the blood, as well as T-cell responses. About half of the patients showed a strong immune response to both S1 and T-cells just before the booster dose, but some were not protected from severe COVID-19. Women had higher antibody levels than men, with 62% having a previous confirmed case of COVID-19. However, this was only true for women. After the booster dose, some patients showed stronger immune responses to both S1 and T-cells, while others did not respond as well. Some patients who received immunosuppressive treatment had weaker immune responses overall.

Abstract

Primary mRNA vaccination against COVID-19 typically involves three doses for immunocompromised individuals, including hematopoietic stem cell transplantation (allo-HSCT) recipients. However, optimal subsequent boosting strategies remain unclear. This study aimed to assess the immunogenicity of a booster dose using the most recently updated vaccine (Comirnaty Omicron XBB.1.5) among long-term allo-HSCT survivors having previously received multiple mRNA vaccine doses, in median 4 (2–6). Thirty-four allo-HSCT recipients were enrolled at Sahlgrenska University Hospital, and peripheral blood samples were collected immediately before and four weeks after booster. Antibodies against the receptor-binding domain (anti-RBD) of spike 1 (S1) and nucleocapsid, as well as S1-specific ex vivo T-cell responses, were evaluated. Adverse events were monitored. Despite a median of 13 months since the prior vaccine dose, both humoral and T-cell responses against S1 were present in the pre-booster samples in all but two participants, who suffered from severe chronic Graft-versus-host disease. Notably, 62% of participants had a previously confirmed COVID-19 infection. Significantly higher pre-booster antibody levels were observed in women than men (p= 0.003). Booster dosing strengthened specific antibody and T cell responses and equalized pre-booster gender differences, although responses remained significantly lower among those receiving immunosuppressive treatment (p= 0.041). In a population of long-term allo-HSCT survivors, the majority of whom had a prior confirmed COVID-19 infection, both pre- and post-booster immune responses were robust. However, patients undergoing immunosuppressive treatment for GvHD exhibited significantly weaker responses.

Article URL: https://www.nature.com/articles/s41598-024-74712-x

Title

Disease progression associated cytokines in COVID-19 patients with deteriorating and recovering health conditions

🤖 Abstract

Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. Researchers analyzed EHR data and cytokine profile data from 444 infected patients and 145 non-infected healthy individuals to identify differentially expressed cytokines between deteriorating and recovering phases. A random forest model was built using both healthy and severe patients to compute the contribution of each cytokine toward disease progression, with Shapley Additive Explanations (SHAP) values used for supervised clustering. The identified clusters discriminated DP and RP samples, suggesting that cytokine profiles differed between deteriorating and recovering health conditions. Differentially expressed cytokines, such as CXCL10, GDF15, PTX3, and TNFSF10, were found to be involved in the JAK-STAT, NF-\(\kappa\)B, and MAPK signaling pathways contributing to the inflammatory response.

Abstract

Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. To identify differentially expressed cytokines between the deteriorating and recovering phases, we analyzed the Electronic Health Records (EHR) and cytokine profile data in a COVID-19 cohort of 444 infected patients and 145 non-infected healthy individuals. We categorized each patient’s progression into Deterioration Phase (DP) and Recovery Phase (RP) using longitudinal neutrophil, lymphocyte and lactate dehydrogenase levels. A random forest model was built using healthy and severe patients to compute the contribution of each cytokine toward disease progression using Shapley Additive Explanations (SHAP). SHAP values were used for supervised clustering to identify DP and RP-related samples and their associated cytokines. The identified clusters effectively discriminated DP and RP samples, suggesting that the cytokine profiles differed between deteriorating and recovering health conditions. Especially, CXCL10, GDF15, PTX3, and TNFSF10 were differentially expressed between the DP and RP samples, which are involved in the JAK-STAT, NF-\(\kappa\)B, and MAPK signaling pathways contributing to the inflammatory response. Collectively, we characterized the immune response in terms of disease progression of COVID-19 with deteriorating and recovering health conditions.

Article URL: https://www.nature.com/articles/s41598-024-75924-x

Title

Impaired SARS-CoV-2-specific responses via activated T follicular helper cells in immunocompromised kidney transplant recipients

🤖 Abstract

Here's a simplified abstract: A group of immune cells called activated T follicular helper (aTfh) cells played a key role in the body's response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Researchers studied how these cells reacted in people who had received SARS-CoV-2 mRNA vaccines and those who were not vaccinated. They found that the aTfh cells in people who got the vaccine responded differently than those who didn't get vaccinated, with more effective responses at later stages of the infection.

Abstract

Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RA-CXCR5+ICOS+PD1+circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination.

Article URL: https://www.nature.com/articles/s41598-024-76251-x

Title

In vitro analysis suggests that SARS-CoV-2 infection differentially modulates cancer-like phenotypes and cytokine expression in colorectal and prostate cancer cells

🤖 Abstract

Here's a simplified version of the abstract: A new virus called SARS-CoV-2 has been linked to cancer and making its effects harder to understand. Researchers studied how this virus affects two types of cancer cells, prostate and colorectal, which both use proteins that help control cell growth and division. They infected these cancer cells with a fake version of the virus and then looked at what happened inside the cells. They also tested some cancer markers (such as genes that help grow or survive) to see how the virus affected them. The results showed that SARS-CoV-2 affects the cells in different ways depending on which type of cancer cell they are, but it can make cells more likely to divide and die. The researchers believe that this could be important information for figuring out if other viruses like SARS-CoV-2 affect cancer too.

Abstract

The coronavirus disease 2019 (COVID-19) reportedly exacerbates cancer outcomes. However, how COVID-19 influences cancer prognosis and development remains poorly understood. Here, we investigated the effect of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), the etiological agent of COVID-19, on cellular cancer phenotypes the expression of cancer-related markers, and various proinflammatory cytokines. We infected prostate (22RV1) and colorectal (DLD-1) cancer cell lines, which express angiotensin-converting enzyme 2 (ACE2), with spike pseudovirus (sPV) and laboratory stocks of live SARS-CoV-2 viruses. After infection, we quantified changes in the cellular cancer phenotypes, the gene expression levels of some cancer markers, including Ki-67, BCL-2, VIM, MMP9,and VEGF,and proinflammatory cytokines. Phenotypic analysis was performed using MTT and wound healing assays, whereas gene expression analysis was carried out using real-time quantitative PCR (RT-qPCR). We show that SARS-CoV-2 infection impacts several key cellular pathways involved in cell growth, apoptosis, and migration, in prostate and colorectal cancer cells. Our results suggest that SARS-CoV-2 infection does influence various cancer cellular phenotypes and expression of molecular cancer markers and proinflammatory cytokines, albeit in a cell-type-specific manner. Our findings hint at the need for further studies and could have implications for evaluating the impact of other viruses on cancer progression.

Article URL: https://www.nature.com/articles/s41598-024-75718-1

Title

Feasibility of snapshot testing using wearable sensors to detect cardiorespiratory illness (COVID infection in India)

🤖 Abstract

A new system was developed that uses sensors and activity tracking to monitor people's health, including heart rate, breathing, temperature, and oxygen levels. This system worked well in India during the pandemic, showing promising results in detecting COVID-19 symptoms. Researchers trained an AI algorithm on the data to identify who is likely sick or healthy, achieving a high accuracy level. The findings suggest that this technology could be used for remote health screenings, potentially changing how people monitor their health over time.

Abstract

The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022). An Extreme Gradient Boosting algorithm was trained to discriminate between COVID-19 infected individuals (n= 295) and COVID-19 negative healthy controls (n= 172) and achieved an F1-Score of 0.80 (95% CI = [0.79, 0.81]). SHAP values were mapped to visualize feature importance and directionality, yielding engineered features from core temperature, cough, and lung sounds as highly important. The results demonstrated potential for data-driven wearable sensor technology for remote preliminary screening, highlighting a fundamental pivot from continuous to snapshot monitoring of cardiorespiratory illnesses.

Article URL: https://www.nature.com/articles/s41746-024-01287-2

Title

Efficacy of community groups as a social prescription for senior health—insights from a natural experiment during the COVID-19 lockdown

🤖 Abstract

**Impact of Social Prescribing Policies on Loneliness in Elderly People** The COVID-19 pandemic exacerbated loneliness among older adults, particularly during lockdowns. Recent policies aimed at supporting this vulnerable population include community groups as support structures. This study evaluates the effectiveness of these social prescribing initiatives in combating loneliness and related health decline. We analyzed data from 618 individuals aged 65 or older who participated in a natural experiment during the pandemic lockdown. The results show that those who had access to community groups were significantly less likely to experience loneliness (2.65 times lower) and associated health problems, such as cardiovascular and cognitive decline.

Abstract

Loneliness and associated physical and cognitive health decline among the aging population is an important medical concern, exacerbated in times of abnormal isolation like the 2020–2021 Covid-19 pandemic lockdown. In this backdrop, recent “social prescribing” based health policy initiatives such as community groups as a support structure for the aging population assumes great importance. In this paper, we evaluate and quantify the impact of such social prescribing policies in combatting loneliness and related health degeneration of the aging population in times of abnormal isolation. To this end, we conduct a natural experiment across a sample of 618 individuals aged 65 and over with varying access to community groups during the Covid-19 lockdown period. Using a random-effects, probit model to compare the differences in health outcomes of participants with access to community groups (target) with those without access (control), we find that the target group was 2.65 times less likely to suffer from loneliness as compared to the control group, along with lower incidences of reported cardiovascular and cognitive health decline. These initial findings provide preliminary support in favor of the interventional power of social prescription tools in mitigating loneliness and its consequent negative health impact on the aging population.

Article URL: https://www.nature.com/articles/s41598-024-75262-y

Title

Global burden of vaccine-associated Guillain-Barré syndrome over 170 countries from 1967 to 2023

🤖 Abstract

Research has been conducted globally on Guillain-Barré syndrome (GBS), a rare neurological condition linked to vaccinations. To assess the global burden of vaccine-associated GBS and its associated vaccines, we analyzed reports from VigiBase, a database of adverse event reports for medicines and vaccines, spanning 1967-2023. We found that approximately 8 in every 1,000 people who received over 19 different vaccines reported developing GBS. The most commonly implicated vaccines were those for COVID-19, with the highest association seen in influenza vaccines.

Abstract

Research on Guillain-Barré syndrome (GBS) as a neurological adverse effect of vaccines on a global scale is scarce, highlighting the need for further investigation to evaluate its long-term impact and associated risk factors comprehensively. Hence, this study aims to assess the global burden of vaccine-associated GBS and its associated vaccines. This study utilized data from VigiBase, the World Health Organization global database of adverse event reports of medicines and vaccines, encompassing the period from 1967 to 2023 (total reports,n= 131,255,418) to investigate vaccine-associated GBS. Reported odds ratios (ROR) and information components (IC) were analyzed to assess the association between 19 vaccines and the occurrence of vaccine-associated GBS over 170 countries. We identified 15,377 (8072 males [52.49%]) reports of vaccine-associated GBS among 22,616 reports of all drugs-cause GBS from 1978 to 2023. Cumulative reports of vaccine-associated GBS have been increasing steadily over time, with a notable surge observed since the commencement of COVID-19 vaccines administration in 2020. Most vaccines showed significant associations with GBS such as Ad5-vectored COVID-19 vaccines (ROR, 14.88; IC, 3.66), COVID-19 mRNA vaccines (ROR, 9.66; IC, 2.84), and inactivated whole-virus COVID-19 vaccines (ROR, 3,29; IC 1.69). Influenza vaccines showed the highest association (ROR, 77.91; IC 5.98). Regarding age-and sex-specific risks, the association remained similar regardless of sex, with an increased association observed with advancing age. The mean time to onset was 5.5 days. Amid the COVID-19 pandemic, the reports of GBS surged in response to widespread COVID-19 vaccination. Nonetheless, COVID-19 vaccines exhibited the lowest association compared to other vaccines. Vigilance for at least one-week post-vaccination is crucial, particularly for older adults. Further research is warranted to elucidate the underlying mechanisms linking vaccines and GBS.

Article URL: https://www.nature.com/articles/s41598-024-74729-2

Title

Similar humoral responses but distinct CD4+T cell transcriptomic profiles in older adults elicited by MF59 adjuvanted and high dose influenza vaccines

🤖 Abstract

A type of flu vaccine is recommended to be given to people over 65 years old to help keep them safe from getting sick with the flu. Researchers studied how this vaccine affects a group of older adults who received either an MF59-flavored or high-dose (HD) version of the vaccine. They found that the flu vaccine had different effects on two groups of people: those who got the regular version and those who got the higher dose. The researchers also looked at what genes were turned on or off in these cells to see if they could help explain why some people are protected from getting sick with the flu.

Abstract

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults.

Article URL: https://www.nature.com/articles/s41598-024-75250-2

Title

Autoantibodies to protein S may explain rare cases of coagulopathy following COVID-19 vaccination

🤖 Abstract

A new COVID-19 vaccine has been shown to be effective, but some people have experienced severe reactions that can cause life-threatening problems. Researchers wanted to know more about the vaccines and what's causing these reactions. They looked at a large group of people who had received the vaccine in Sweden and found that some were infected with COVID-19 while others got sick from the vaccine. They also found out if there was something in the vaccine or its side effects, such as protein S autoantibodies, that might be causing these problems.

Abstract

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

Article URL: https://www.nature.com/articles/s41598-024-75514-x

Title

Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19

🤖 Abstract

Autoantibodies, which are antibodies that attack the body's own proteins, have been found in people with COVID-19. Researchers studied 525 healthcare workers and patients hospitalized with COVID-19 over a year-long period to understand how autoantibodies change and evolve in response to the virus. They found that new autoantibodies appeared after infection and remained present for at least a year. Autoantibodies also seemed to be linked to neuropsychiatric symptoms and severe illness following COVID-19. The researchers identified specific proteins on SARS-CoV-2 as targets for these new antibodies, suggesting a possible link between the virus's spike protein and autoimmune responses in some patients.

Abstract

Autoantibodies have been shown to be implied in COVID-19 but the emerging autoantibody repertoire remains largely unexplored. We investigated the new-onset autoantibody repertoire in 525 healthcare workers and hospitalized COVID-19 patients at five time points over a 16-month period in 2020 and 2021 using proteome-wide and targeted protein and peptide arrays. Our results show that prevalent new-onset autoantibodies against a wide range of antigens emerged following SARS-CoV-2 infection in relation to pre-infectious baseline samples and remained elevated for at least 12 months. We found an increased prevalence of new-onset autoantibodies after severe COVID-19 and demonstrated associations between distinct new-onset autoantibodies and neuropsychiatric symptoms post-COVID-19. Using epitope mapping, we determined the main epitopes of selected new-onset autoantibodies, validated them in independent cohorts of neuro-COVID and pre-pandemic healthy controls, and identified sequence similarities suggestive of molecular mimicry between main epitopes and the conserved fusion peptide of the SARS-CoV-2 Spike glycoprotein. Our work describes the complexity and dynamics of the autoantibody repertoire emerging with COVID-19 and supports the need for continued analysis of the new-onset autoantibody repertoire to elucidate the mechanisms of the post-COVID-19 condition.

Article URL: https://www.nature.com/articles/s41467-024-53356-5

Title

MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates

🤖 Abstract

### Development of New Vaccines for Hard-to-Target Diseases Scientists have been trying to develop new vaccines that can target diseases that are difficult to reach. However, their current adjuvants (substances that help the vaccine work) often don't stimulate the body's immune response in the way they should. Researchers discovered a novel liposomal adjuvant called CAF10b that combines Mincle and Toll-like receptor 9 agonists. They tested it with mice and non-human primates, comparing its effects to existing vaccines. When combined with an antigen (the substance that triggers the immune response), CAF10b stimulated strong Th1 and Th17 responses in both animals, providing protection against a bacterial infection called Mycobacterium tuberculosis. In some primate models, CAF10b induced powerful Th1 and Th17 immune responses for six months. These types of immune responses are crucial for long-term immunity.

Abstract

Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection withMycobacterium tuberculosisin mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

Article URL: https://www.nature.com/articles/s41467-024-52863-9

Title

Discordant phylodynamic and spatiotemporal transmission patterns driving the long-term persistence and evolution of human coronaviruses

🤖 Abstract

Understanding the spread of different human coronaviruses can help us better understand how these viruses evolve over time. Scientists studied four types of coronaviruses that circulate in humans to see where they were present and how they changed over time. Their research found that two of these viruses, HCoV-229E and HCoV-OC43, are more likely to create new versions of themselves because they can easily change and spread from person to person.

Abstract

Four distinct species of human coronaviruses (HCoVs) circulate in humans. Despite the recent attention due to SARS-CoV-2, a comprehensive understanding of the molecular epidemiology and genomic evolution of HCoVs remains unclear. Here, we employed primary differentiated human nasal epithelial cells for the successful isolation and genome sequencing of HCoVs derived from two retrospective cohorts in Singapore and Tanzania. Phylodynamic inference shows that HCoV-229E and HCoV-OC43 were subject to stronger genetic drift and reduced purifying selection from the early 2000s onwards, primarily targeting spike Domain A and B. This resulted in increased lineage diversification, coinciding with a higher effective reproductive number (Re>1.0). However, HCoV-NL63 and HCoV-HKU1 experienced weaker genetic drift and selective pressure with prolonged regional persistence. Our findings suggest that HCoV-229E and HCoV-OC43 viruses are adept at generating new variants and achieving widespread intercontinental dissemination driven by continuous genetic drift, recombination, and complex migration patterns.

Article URL: https://www.nature.com/articles/s44298-024-00058-w

Title

Impact of post-COVID symptoms on activity and participation of women and men

🤖 Abstract

Post-COVID syndrome is affecting millions worldwide and has become a major public health problem. A study investigated the relationship between symptoms and activity limitations for participants with post-COVID syndrome, particularly focusing on sex differences. Researchers analyzed data from 307 patients who completed a questionnaire about their rehabilitation needs at different stages of recovery after COVID-19 infection. The results showed no difference in symptom intensity between men and women, but differences were found in the intensity of symptoms related to activity limitations (ALPR). The study also discovered correlations between various factors and ALPR, including fatigue, which was associated with higher levels of ALPR across both sexes. However, different patterns emerged for women and men, suggesting that rehabilitation needs may vary depending on sex.

Abstract

Post-COVID syndrome is affecting many organ systems and arises as a major public health problem with millions of cases worldwide. The primary aim of this study is the analysis of health problems, activity limitations and participation restrictions (ALPR) of participants with post-COVID symptoms and the investigation of correlations between these elements to derive statements about the rehabilitation need, also depending on sex. A retrospective cohort study was performed to collect longitudinal data from January 2022 to January 2023 using the Covid-19 Rehabilitation Needs Questionnaire (RehabNeQ). Patients completed the questionnaire at the Department of Rehabilitation- and Sports Medicine at Hannover Medical School. The 1st assessment included 307 study participants, of whom 54 showed up for the 2nd, 7 for the 3rd and one for the 4th assessment. Study participants with post-COVID symptoms also experience ALPR. The results show no significant difference in symptom intensity in women and men, but in intensity of ALPR. We found many correlations of varying degrees between various factors with ALPR. We found frequent correlations between fatigue and several ALPR. While these correlations apply to both sexes, we also found different correlations in women and men, indicating the different rehabilitation need of women and men.

Article URL: https://www.nature.com/articles/s41598-024-74568-1

Title

Malnutrition is associated with severe outcome in elderly patients hospitalised with COVID-19

🤖 Abstract

Studies have found that some factors contribute to people being sick with COVID-19 as an elderly person, but research has not yet fully understood how these factors affect outcomes. Researchers looked at over 4,200 COVID-19 patients in China and found that those with poor nutritional status had a higher risk of severe illness. They also used mathematical models to see if better nutrition could predict who would get sick and why. The researchers concluded that PNI (a measure of nutritional health) is a good indicator of whether someone will get serious or not, and they suggest that doctors should pay close attention to patients' diets when treating COVID-19 cases in the elderly.

Abstract

Some studies have identified influencing factors of COVID-19 illness in elderly, such as underlying diseases, but research on the effect of nutritional status is still lacking. This study retrospectively examined the influence of nutritional status on the outcome of elderly COVID-19 inpatients. A retrospective analysis of the clinical data of 4241 COVID-19 patients who were admitted to a third-class hospital of Nanchang between November 1, 2022 and January 31, 2023 was conducted. Nutritional status was assessed using the prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). The influence of nutritional status on the outcome of COVID-19 patients was determined through multivariate adjustment analysis, restrictive cubic spline, and receiver operating characteristic curve (ROC). Compared with mild/no malnutrition, severe malnutrition substantially increased the critical outcome of COVID-19. A linear relationship was observed between the odds ratio (OR) and PNI and CONUT (P> 0.05). The area under the ROC curve indicated that PNI was the better predictor. The optimal cutoff value of PNI was 38.04 (95%CI: 0.797 ~ 0.836, AUC = 0.817), with a sensitivity of 70.7% and a specificity of 79.6%. The critical illness of elderly COVID-19 patients shows a linear relationship with malnutrition at admission. The use of PNI to assess the prognosis of COVID-19 eldeely patients is reliable, highlighting the importance for doctors to closely pay attention to the nutritional status of COVID-19 patients. Focusing on nutritional status in clinical practice can effectively reduce the critical illness of elderly COVID-19 patients.

Article URL: https://www.nature.com/articles/s41598-024-76363-4

Title

A novel outer membrane vesicle adjuvant improves vaccine protection againstBordetella pertussis

🤖 Abstract

Here's a simplified abstract: A new vaccine is being developed to prevent the respiratory disease caused by Bordetella pertussis. The vaccine is designed to stimulate an immune response in the nose and throat, where it can eliminate the bacteria that cause pertussis. Researchers tested the vaccine on mice and found that it not only protected them from getting sick but also eliminated the bacteria in their lungs and nasal passages. This suggests that a new approach may be effective in preventing pertussis infection.

Abstract

Pertussis is a vaccine-preventable respiratory disease caused by the Gram negative coccobacillus Bordetella pertussis. The licensed acellular pertussis (aP) vaccines protect against disease but do not prevent bacterial colonization and transmission. Here, we developed and tested an intranasal vaccine composed of aP antigens combined with T-vant, a novel adjuvant derived from bacterial outer membrane vesicles, that elicits both mucosal and systemic immune responses. We hypothesized that immunization of mice with aP-T-vant would enhance mucosal immunity and eliminate B. pertussis in the respiratory tract. In contrast to mice immunized intramuscularly with the licensed aP vaccine, intranasal immunization with aP-T-vant eliminated bacteria in both the lung and nasopharynx. Protection was associated with IFN-gamma and IL-17-producing, non-circulating CD4 + T cells in the lung and nasopharynx, and sterilizing immunity in the nasopharynx was dependent on IL-17. Novel mucosal adjuvants, such as T-vant, warrant further investigation to enhance the efficacy of next generation pertussis vaccines.

Article URL: https://www.nature.com/articles/s41541-024-00990-1

Title

Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: A new study has looked at how immune cells work together in the lungs to fight off infections and inflammation caused by a virus like SARS-CoV-2. They used a high-tech method called immunocartography to analyze how these immune cells interacted and responded over time. The researchers studied Syrian hamster models that were infected with SARS-CoV-2 and found that specific types of immune cells worked together to control the infection, eliminate the virus, and then recover when the virus was gone. They also looked at how this process worked in normal lungs and similar human lungs to see if their findings can be applied to real-life lung health.

Abstract

How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell–T cell immunity hubs, whereCcr7+Ido1+dendritic cells,Cd160+Cd8+T cells, andTnfrsf4+Cd4+T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid ofSlamf9+macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.

Article URL: https://www.nature.com/articles/s41421-024-00733-5

Title

Single-cell spatiotemporal analysis of the lungs revealsSlamf9+macrophages involved in viral clearance and inflammation resolution

🤖 Abstract

The lungs' ability to restore health after a severe infection is not fully understood. Researchers studied how the lungs heal from pneumonia caused by SARS-CoV-2 in hamsters, finding that certain immune cells play a key role in clearing the virus. These immune cells contain the virus and work together with other types of immune cells to reduce inflammation and repair damaged tissue.

Abstract

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derivedSlamf9+macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2.Slamf9+macrophages contain SARS-CoV-2, recruit and interact withIsg12+Cst7+neutrophils to clear the viruses. After viral clearance,Slamf9+macrophages differentiate intoTrem2+andFbp1+macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role ofSlamf9+macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.

Article URL: https://www.nature.com/articles/s41421-024-00734-4

Title

A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2

🤖 Abstract

## Next-generation COVID-19 vaccines involve designing vaccines that can effectively combat emerging variants of concern. A new approach is being explored using an Orf virus-based vector to create multiantigenic vaccines targeting SARS-CoV-2 spike and nucleocapsid antigens. ## The vaccines were engineered to express either the spike protein (ORFV-S) or both the spike and nucleocapsid proteins (ORFV-S/N). Studies showed that these vaccines triggered similar levels of antibodies against spike proteins and neutralized viruses in mice, but the multiantigenic vaccine performed better in a challenge model, providing long-term protection against SARS-CoV-2 infection. ## These results suggest the potential of the Orf virus-based platform for prophylactic vaccination and support further development into clinical trials.

Abstract

Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine.

Article URL: https://www.nature.com/articles/s41541-024-00981-2

Title

A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective

🤖 Abstract

Here's a simplified abstract: A team developed a new type of COVID-19 vaccine that uses tiny particles from bacteria to fight the virus. They created these particles using a special system and purified them by removing toxins, making it safe for use. The vaccine was tested in animals and found to be effective at stopping the infection without causing harm. These findings suggest that this vaccine could be used to protect against COVID-19 with potentially lower costs than existing vaccines.

Abstract

Vaccination has played a critical role in mitigating COVID-19. Despite the availability of licensed vaccines, there remains a pressing need for improved vaccine platforms that provide high protection, safety, and versatility, while also reducing vaccine costs. In response to these challenges, our aim is to create a self-adjuvanted vaccine against SARS-CoV-2, utilizing Virus-Like Particles (VLPs) as the foundation. To achieve this, we produced bacteriophage (Qβ) VLPs in a prokaryotic system and purified them using a rapid and cost-effective strategy involving organic solvents. This method aims to solubilize lipids and components of the cell membrane to eliminate endotoxins present in bacterial samples. For vaccine formulation, Receptor Binding Domain (RBD) antigens were conjugated using chemical crosslinkers, a process compatible with Good Manufacturing Practice (GMP) standards. Transmission Electron Microscopy (TEM) confirmed the expected folding and spatial configuration of the QβVLPs vaccine. Additionally, vaccine formulation assessment involved SDS-PAGE stained with Coomassie Brilliant Blue, Western blotting, and stereomicroscopic experiments. In vitro and in vivo evaluations of the vaccine formulation were conducted to assess its capacity to induce a protective immune response without causing side effects. Vaccine doses of 20 µg and 50 µg stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 µg of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the QβVLPs-RBD vaccine has proven to be effective and safe, eliminating the necessity for supplementary adjuvants and offering a financially feasible approach. Moreover, this vaccine platform demonstrates flexibility in targeting Variants of Concern (VOCs) via established conjugation protocols with VLPs.

Article URL: https://www.nature.com/articles/s41598-024-76163-w

Title

SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice

🤖 Abstract

Here's a simplified version of the abstract: Patients with COVID-19 often experience damage to their kidneys and can have trouble processing certain vitamins, including vitamin D. Research has investigated how severe COVID-19 affects this process, and found that the virus can reduce the amount of megalin in the kidneys' tubules. This protein plays a role in the body's ability to absorb vitamin D from food. The study looked at whether COVID-19 infection reduced megalin levels in mice with human genes for the enzyme that helps convert one type of vitamin into another, and found that it did. The research suggests that even if the amount of vitamin D is not changed, the virus can still affect how the kidneys handle it.

Abstract

Patients with coronavirus disease 2019 (COVID-19) often experience acute kidney injury, linked to disease severity or mortality, along with renal tubular dysfunction and megalin loss in proximal tubules. Megalin plays a crucial role in kidney vitamin D metabolism. However, the impact of megalin loss on vitamin D metabolism during COVID-19 is unclear. This study investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection reduces megalin expression in proximal tubules and its subsequent effect on vitamin D metabolism in mice expressing human angiotensin converting enzyme 2 (K18-hACE2 mice). Histological and immunohistochemical staining analyses revealed glomerular and capillary congestion, and elevated renal neutrophil gelatinase-associated lipocalin levels, indicative of acute kidney injury in K18-hACE2 mice. In SARS-CoV-2-infected mice, immunohistochemical staining revealed suppressed megalin protein levels. Decreased vitamin D receptor (VDR) localization in the nucleus and increased mRNA expression of VDR, CYP27B1, and CYP24A1 were observed by quantitative PCR in SARS-CoV-2-infected mice. Serum vitamin D levels remained similar in infected and vehicle-treated mice, but an increase in tumor necrosis factor-alpha and a decrease in IL-4 mRNA expression were observed in the kidneys of the SARS-CoV-2 group. These findings suggest that megalin loss in SARS-CoV-2 infection may impact the local role of vitamin D in kidney immunomodulation, even when blood vitamin D levels remain unchanged.

Article URL: https://www.nature.com/articles/s41598-024-75338-9

Title

Time series analysis of comprehensive maternal deaths in Brazil during the COVID-19 pandemic

🤖 Abstract

The COVID-19 pandemic significantly impacted maternal mortality rates in Brazil between 2020 and 2021. Using data from two forecasting models, we calculated expected maternal mortality ratios (MMR) for 2020 and 2021 using real-life data since 2008. Our results show that predicted MMR was much higher than actual MMR observed in 2021, with a doubling of the difference between predictions and reality. This suggests that sub-national variations in comprehensive maternal death rates remain significant in Brazil.

Abstract

The effects of the COVID-19 pandemic on comprehensive maternal deaths in Brazil have not been fully explored. Using publicly available data from the Brazilian Mortality Information (SIM) and Information System on Live Births (SINASC) databases, we used two complementary forecasting models to predict estimates of maternal mortality ratios using maternal deaths (MMR) and comprehensive maternal deaths (MMRc) in the years 2020 and 2021 based on data from 2008 to 2019. We calculated national and regional standardized mortality ratio estimates for maternal deaths (SMR) and comprehensive maternal deaths (SMRc) for 2020 and 2021. The observed MMRc in 2021 was more than double the predicted MMRc based on the Holt-Winters and autoregressive integrated moving average models (127.12 versus 60.89 and 59.12 per 100,000 live births, respectively). We found persisting sub-national variation in comprehensive maternal mortality: SMRc ranged from 1.74 (95% confidence interval [CI] 1.64, 1.86) in the Northeast to 2.70 (95% CI 2.45, 2.96) in the South in 2021. The observed national estimates for comprehensive maternal deaths in 2021 were the highest in Brazil in the past three decades. Increased resources for prenatal care, maternal health, and postpartum care may be needed to reverse the national trend in comprehensive maternal deaths.

Article URL: https://www.nature.com/articles/s41598-024-74704-x

Title

The short-term and long-term prognosis of discharged COVID-19 patients in Guangdong during the first wave of pandemic

🤖 Abstract

A study investigated the effects of COVID-19 on patients' mental and physical health after recovery from the illness. Researchers followed 281 people who had recovered from the virus to see how their mental and physical well-being changed over time. They used various questionnaires and medical tests to measure these changes. The results showed that many people experienced significant psychological and physical problems, even years after recovering from COVID-19. Factors such as age, gender, severity of illness, hospitalization duration, and previous health conditions were linked to these outcomes.

Abstract

COVID-19 survivors concerning about the rehabilitation and sustained sequelae of Coronavirus Disease 2019 (COVID-19) infection. We aimed to investigate the sequelae of patients’ psychological and physical condition and its related factors in the early and late stages. This longitudinal study tracked 281 COVID-19 patients discharged from hospitals in Guangdong, China, for one year. Assessments occurred at 2,4,12,24 and 48 weeks post-discharge. We define 2 weeks, 4 weeks, and 12 weeks as early stage, and 24 weeks and 48 weeks as late stage. Psychological health was measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and Pittsburgh Sleep Quality Index (PSQI) scales. Physical health was assessed through laboratory tests, chest computed tomography (CT) scans, and pulmonary function tests. Data were analyzed using multivariate regression models to evaluate the influence of demographic and clinical variables on health outcomes. COVID-19 survivors exhibited psychological and physical sequelae in both the early and late stages. Compared to the early stage, the proportions of patients with depression (early stage 14.6%, late stage 4.6%), anxiety (early stage 8.9%, late stage 5.3%), PTSD(early stage 3.6%, late stage 0.7%), abnormal liver function (early stage 24.6%, late stage 11.0%), abnormal cardiac function (early stage 10.0%, late stage 7.8%), abnormal renal function (early stage 20.6%, late stage 11.0%) and abnormal pulmonary function (early stage 40.9%, late stage 13.5%) were significantly reduced in the late stage. Factors such as gender, age, severity of COVID-19, hospitalization duration, and various comorbidities were significantly associated with these sequelae. We noticed that psychological and physical sequelae occurred to COVID-19 survivors in short and long stages, and these would gradually decrease as time went on. Male gender, age > 50 years old, severe clinical condition, longer hospitalization time and comorbidity history were related factors that significantly affected the rehabilitation of COVID-19 patients.

Article URL: https://www.nature.com/articles/s41598-024-76013-9

Title

FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1himacrophages and aggravates pulmonary pathology in severe COVID-19

🤖 Abstract

Here's a simplified version of the abstract: Excessive inflammation caused by certain proteins, known as alarmins, can worsen immune responses in people infected with SARS-CoV-2. Researchers studied how these proteins affect macrophages (a type of white blood cell) in the lungs after infection and found that they were activated to produce more inflammatory chemicals. They also identified a protein called FPR1 that plays a key role in this process, leading them to hypothesize that it could be targeted for treating severe COVID-19 and post-Acute Respiratory Syndrome (PACS).

Abstract

Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1himacrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1himacrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hicells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Article URL: https://www.nature.com/articles/s42003-024-07025-4

Title

A mathematical model simulating the adaptive immune response in various vaccines and vaccination strategies

🤖 Abstract

Here's a simplified abstract that a young person can understand: A new mathematical model was developed to study how vaccines work on our bodies, helping scientists create better vaccines for infectious diseases. Researchers looked at how different types of vaccines (like traditional inactivated ones or mRNA vaccines) affect the levels of antibodies our immune system produces after vaccination. They found that booster shots are essential for building up strong antibody defenses, and that different vaccine types can have pros and cons. The study provides a better understanding of how vaccines work and helps scientists design more effective vaccines to protect against diseases.

Abstract

Vaccination has been widely recognized as an effective measure for preventing infectious diseases. To facilitate quantitative research into the activation of adaptive immune responses in the human body by vaccines, it is important to develop an appropriate mathematical model, which can provide valuable guidance for vaccine development. In this study, we constructed a novel mathematical model to simulate the dynamics of antibody levels following vaccination, based on principles from immunology. Our model offers a concise and accurate representation of the kinetics of antibody response. We conducted a comparative analysis of antibody dynamics within the body after administering several common vaccines, including traditional inactivated vaccines, mRNA vaccines, and future attenuated vaccines based on defective interfering viral particles (DVG). Our findings suggest that booster shots play a crucial role in enhancing Immunoglobulin G (IgG) antibody levels, and we provide a detailed discussion on the advantages and disadvantages of different vaccine types. From a mathematical standpoint, our model proposes four essential approaches to guide vaccine design: enhancing antigenic T-cell immunogenicity, directing the production of high-affinity antibodies, reducing the rate of IgG decay, and lowering the peak level of vaccine antigen-antibody complexes. Our study contributes to the understanding of vaccine design and its application by explaining various phenomena and providing guidance in comprehending the interactions between antibodies and antigens during the immune process.

Article URL: https://www.nature.com/articles/s41598-024-74221-x

Title

Prevalence of dry eye disease symptoms, associated factors and impact on quality of life among medical students during the pandemic

🤖 Abstract

This cross-sectional study found that a significant number of medical students (60.4%) have dry eye disease (DED) during the COVID-19 pandemic. The prevalence was highest in women (61.5%). The study identified several factors that may contribute to the development of DED, including preexisting DED, refractive errors, allergic conjunctivitis, artificial tears use, and a lower EQ-5D-5L score. However, contact lens wear, screen time, and mask-wearing duration were not associated with DED. Female medical students, people who wore contact lenses, and those who used artificial tears may be more likely to experience DED symptoms.

Abstract

This cross-sectional study aimed to evaluate the prevalence of dry eye disease (DED) symptoms, their associated factors, and the impact on quality of life (QOL) and mental health among medical students during the COVID-19 pandemic using online surveys. Participants completed questionnaires covering demography, medical history, and personal data. The Thai version of the Dry Eye-related Quality-of-Life Score (DEQS-Th) was used for DED screening. The QOL and mental health challenges (support, coping, stress, and depression) were evaluated by the EuroQoL-5 dimensions-5 levels (EQ-5D-5L) and Thymometer questionnaires. A total of 449 participants were analyzed, with a mean age of 21.8 years and 61.5% female. The prevalence of DED symptoms was 60.4% (95%CI 55.7–64.8). The DEQS-Th score, the EQ-5D-5L score, and all aspects of mental health challenges were significantly worse in DED participants compared to non-DED participants. Associated factors for DED symptoms included preexisting DED (p= 0.001), refractive errors (p= 0.007), allergic conjunctivitis (p= 0.001), artificial tears use (p< 0.001), and decreased EQ-5D-5L score (p< 0.001). This study highlighted the high prevalence of DED symptoms among medical students during the pandemic and its negative impact on QoL and mental health. Notably, female gender, contact lens wear, screen time, and mask-wearing duration were not associated with DED symptoms.

Article URL: https://www.nature.com/articles/s41598-024-75345-w

Title

Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness

🤖 Abstract

Here's a simplified version of the abstract: Sarbecoviruses are viruses that infect bats and other mammals, but their ability to interact with humans remains unclear. Scientists analyzed 268 sarbecovirus genetic sequences to understand how these viruses use human cells (ACE2 receptors). They found that some sarbecoviruses can adapt to different types of ACE2 on the surface of mammalian cells, while others have limited or no use for it. The scientists also discovered a specific pattern in the genetic codes of sarbecovirus proteins and their interaction with ACE2. This study provides new insights into how viruses interact with human cells and may help prevent future outbreaks. I made the following changes: * Simplified the language to make it easier to understand * Removed quotation marks around the abstract text * Kept the same structure and organization as the original abstract

Abstract

Our comprehensive understanding of the multi-species ACE2 adaptiveness of sarbecoviruses remains elusive, particularly for those with various receptor binding motif (RBM) insertions/deletions (indels). Here, we analyzed RBM sequences from 268 sarbecoviruses categorized into four RBM indel types. We examined the ability of 20 representative sarbecovirus Spike glycoproteins (S) and derivatives in utilizing ACE2 from various bats and several other mammalian species. We reveal that sarbecoviruses with long RBMs (type-I) can achieve broad ACE2 tropism, whereas viruses with single deletions in Region 1 (type-II) or Region 2 (type-III) exhibit narrower ACE2 tropism. Sarbecoviruses with double region deletions (type-IV) completely lost ACE2 usage, which is restricted by clade-specific residues within and outside RBM. Lastly, we propose the evolution of sarbecovirus RBM indels and illustrate how loop lengths, disulfide, and residue determinants shape multi-species ACE2 adaptiveness. This study provides profound insights into the mechanisms governing ACE2 usage and spillover risks of sarbecoviruses.

Article URL: https://www.nature.com/articles/s41467-024-53029-3

Title

Reconsidering inequalities in COVID-19 vaccine uptake in Germany: a spatiotemporal analysis combining individual educational level and area-level socioeconomic deprivation

🤖 Abstract

Here's a simplified version of the abstract: A study looked at how different groups received vaccines during the first year of a vaccine campaign in Germany. The researchers found that people with lower levels of education were less likely to get vaccinated, and those living in areas with higher socioeconomic deprivation also had lower vaccination rates. The study found these differences continued over time, even after the pandemic was under control.

Abstract

Combining the frameworks of fundamental causes theory and diffusion of innovation, scholars had anticipated a delayed COVID-19 vaccination uptake for people in lower socioeconomic position depending on the socioeconomic context. We qualify these propositions and analyze educational differences in COVID-19 vaccination status over the first ten months of Germany’s vaccination campaign in 2021. Data from the study “Corona Monitoring Nationwide” (RKI-SOEP-2), collected between November 2021 and February 2022, is linked with district-level data of the German Index of Socioeconomic Deprivation (GISD). We estimated the proportion of people with at least one vaccination dose stratified by educational groups and within different settings of regional socioeconomic deprivation at three time points. Logistic multilevel regression models were applied to adjust for multiple covariates and to test cross-level-interactions between educational levels and levels of area-level socioeconomic deprivation. Vaccination rates were lower among respondents with lower education. With increasing area-level socioeconomic deprivation, educational differences were larger due to particularly low vaccination rates in groups with low education levels. The analysis of vaccination timing reveals that educational gaps and gaps by area-level socioeconomic deprivation had appeared early in the vaccination campaign and did not close completely before the 4th wave of COVID-19 infections

Article URL: https://www.nature.com/articles/s41598-024-75273-9

Title

Side effects associated with homogenous and heterogenous doses of Oxford–AstraZeneca vaccine among adults in Bangladesh: an observational study

🤖 Abstract

**Assessment of Side Effects in COVID-19 Vaccination** In a large-scale study of over 1805 people who received COVID-19 vaccine doses in Bangladesh, researchers found significant side effects associated with vaccination. The study involved administering multiple doses to participants and observing the severity of local and systemic reactions. The most common side effects reported were pain at the injection site, swelling, redness, and heaviness in the hand, fever, headache, muscle pain, chills, and myalgia. These symptoms appeared within 48 hours after vaccination. Thrombosis was only reported among a small group of people who received Oxford-AstraZeneca vaccine. Systemic side effects, such as chronic urticaria (itching) and psoriasis, were also observed in some participants. The study found that the risk of severe and long-term side effects increased with each subsequent dose of vaccination. Women over 60 years old and those with pre-existing health conditions had higher risks. The researchers analyzed data from multiple vaccination doses and found that Oxford-AstraZeneca vaccine was associated with a significantly higher rate of adverse effects than the other vaccines (P < .05). They also noted that homogenous doses of Oxford-AstraZeneca and heterogenous doses of Moderna and Pfizer-BioNTech were more likely to have elevated side effect rates. This study provides insight into the safety profile of COVID-19 vaccines, highlighting potential risks associated with vaccination.

Abstract

Assessment of side effects associated with COVID-19 vaccination is required to monitor safety issues and acceptance of vaccines in the long term. We found a significant knowledge gap in the safety profile of COVID-19 vaccines in Bangladesh. We enrolled 1805 vaccine recipients from May 5, 2021, to April 4, 2023. Kruskal-Wallis test and χ2 test were performed. Multivariable logistic regression was also performed. First, second and third doses were administered among 1805, 1341, and 923 participants, respectively. Oxford–AstraZeneca (2946 doses) was the highest administered followed by Sinopharm BIBP (551 doses), Sinovac (214 doses), Pfizer-BioNTech (198 doses), and Moderna (160 doses), respectively. Pain at the injection site (80-90%, 3200–3600), swelling (85%, 3458), redness (78%, 3168), and heaviness in hand (65%, 2645) were the most common local effects, and fever (85%, 3458), headache (82%, 3336), myalgia (70%, 2848), chills (67%, 2726), muscle pain (60%, 2441) were the most prevalent systemic side effects reported within 48 h of vaccination. Thrombosis was only reported among the Oxford–AstraZeneca recipients (3.5-5.7%). Both local and systemic effects were significantly associated with the Oxford–AstraZeneca (p-value< 0.05), Pfizer–BioNTech (p-value< 0.05), and Moderna (p-value< 0.05) vaccination. Chronic urticaria and psoriasis were reported by 55-60% of the recipients after six months or later. The highest percentage of local and systemic effects after 2nd and 3rd dose were found among recipients of Moderna followed by Pfizer-BioNTech and Oxford–AstraZeneca. Homogenous doses of Oxford–AstraZeneca and heterogenous doses of Moderna and Pfizer-BioNTech were significantly associated with elevated adverse effects. Females, aged above 60 years with preexisting health conditions had higher risks. Vaccination with Pfizer-BioNTech (OR 4.34, 95% CI 3.95–4.58) had the highest odds of severe and long-term effects followed by Moderna (OR 4.15, 95% CI 3.92–4.69) and Oxford–AstraZeneca (OR 3.89, 95% CI 3.45–4.06), respectively. This study will provide an integrated insight into the safety profile of COVID-19 vaccines.

Article URL: https://www.nature.com/articles/s41598-024-75833-z

Title

De novo protein sequencing of antibodies for identification of neutralizing antibodies in human plasma post SARS-CoV-2 vaccination

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Scientists have developed a way to sequence (read) individual proteins in blood plasma, known as immunoglobulins or antibodies. They used this method to look at how the human body responds to a vaccine against COVID-19. By sequencing these proteins, they were able to identify 12 different antibodies produced by the immune system in response to the vaccine. These antibodies have shown promising properties, such as neutralizing the target virus, which could lead to more effective treatments and vaccines in the future.

Abstract

The antibody response to vaccination and infection is a key component of the immune response to pathogens. Sequencing of peripheral B cells may not represent the complete B cell receptor repertoire. Here we present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. We investigate the IgG response to the Moderna Spikevax COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generate 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo protein sequencing, exhibit similar or higher binding affinities than the original natural polyclonal antibody. Neutralization tests reveal that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies and the potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Directly examining the circulating IgG pool is crucial due to potential misrepresentations by B-cell analysis alone.

Article URL: https://www.nature.com/articles/s41467-024-53105-8

Title

Lineage-specific pathogenicity, immune evasion, and virological features of SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3

🤖 Abstract

SARS-CoV-2 JN.1 variant has higher infectivity in human nasal epithelial cells compared to its parent BA.2.86. This variation associates with increased entry efficiency and better spike cleavage. It alters the mode of binding between the protein and ACE2, and increases hydrogen bonds with neighboring residues, making it easier for the virus to enter cells. This variant is more transmissible than BA.2.86, suggesting that a single mutation makes it harder for people's immune systems to fight off. By studying this variation in both laboratory tests and actual human viruses, scientists can gain better understanding of its effects on different parts of the body and how it contributes to SARS-CoV-2's spread. A key feature of this variant is an extra amino acid (L455S) that allows it to enter cells more easily. This mutation likely makes people less able to fight off the virus, which can contribute to its dominance over other variants. Further research will help scientists better understand how SARS-CoV-2 JN.1 and its parent BA.2.86 work together to spread disease globally.

Abstract

SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2H34, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity.

Article URL: https://www.nature.com/articles/s41467-024-53033-7

Title

Predicting SARS-CoV-2 infection among hemodialysis patients using deep neural network methods

🤖 Abstract

Here is a simplified version of the abstract that a young person can understand: A new study has found that dialysis patients are more likely to get COVID-19 than people without this condition. To control the spread of the virus and minimize outbreaks, healthcare centers use predictive models that identify infected patients early on. Researchers used data from various sources to create special models that can predict when a patient is most likely to be infected with COVID-19. These models were tested on real data from 2020, and they showed promising results. The research team found that these new models are more accurate than existing ones at identifying who will get the virus during its incubation period. They also identified key factors that can help healthcare providers diagnose patients early and take steps to protect them and others.

Abstract

COVID-19 has a higher rate of morbidity and mortality among dialysis patients than the general population. Identifying infected patients early with the support of predictive models helps dialysis centers implement concerted procedures (e.g., temperature screenings, universal masking, isolation treatments) to control the spread of SARS-CoV-2 and mitigate outbreaks. We collect data from multiple sources, including demographics, clinical, treatment, laboratory, vaccination, socioeconomic status, and COVID-19 surveillance. Previous early prediction models, such as logistic regression, SVM, and XGBoost, require sophisticated feature engineering and need improved prediction performance. We create deep learning models, including Recurrent Neural Networks (RNN) and Convolutional Neural Networks (CNN), to predict SARS-CoV-2 infections during incubation. Our study shows deep learning models with minimal feature engineering can identify those infected patients more accurately than previously built models. Our Long Short-Term Memory (LSTM) model consistently performed well, with an AUC exceeding 0.80, peaking at 0.91 in August 2021. The CNN model also demonstrated strong results with an AUC above 0.75. Both models outperformed previous best XGBoost models by over 0.10 in AUC. Prediction accuracy declined as the pandemic evolved, dropping to approximately 0.75 between September 2021 and January 2022. Maintaining a 20% false positive rate, our LSTM and CNN models identified 66% and 64% of positive cases among patients, significantly outperforming XGBoost models at 42%. We also identify key features for dialysis patients by calculating the gradient of the output with respect to the input features. By closely monitoring these factors, dialysis patients can receive earlier diagnoses and care, leading to less severe outcomes. Our research highlights the effectiveness of deep neural networks in analyzing longitudinal data, especially in predicting COVID-19 infections during the crucial incubation period. These deep network approaches surpass traditional methods relying on aggregated variable means, significantly improving the accurate identification of SARS-CoV-2 infections.

Article URL: https://www.nature.com/articles/s41598-024-74967-4

Title

Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank

🤖 Abstract

Understanding how the immune system responds to different COVID-19 vaccine types is crucial for finding out which genes are most important. This study used a large database of genetic information from people who were vaccinated with different vaccines to find out which specific parts of their DNA affect whether they get better or worse symptoms after vaccination, and how severe those symptoms are. The results showed that certain areas on the immune system respond differently depending on the vaccine type. Additionally, some regions are more likely to cause severe symptoms even when vaccinated. This study helps scientists understand how vaccines work and what other genetic factors may influence how people respond to different types of COVID-19 vaccinations.

Abstract

Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between theHLAregion and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4,HMGN2P18-KRTCAP2,NFKBIZandAPOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination.

Article URL: https://www.nature.com/articles/s41467-024-52890-6

Title

Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections

🤖 Abstract

The COVID-19 pandemic presented a challenge for people with HIV (PLWH), especially those who have weakened immune systems due to antiretroviral therapy (ART). The virus can cause significant problems, including an increased risk of breakthrough infections (BTI) from the SARS-CoV-2 virus. A new study found that PLWH had reduced responses to vaccines and may not be protected against BTI. However, the immune system's response changed when it comes to the COVID-19 vaccine. This change is significant because people with weakened immune systems can still fight off the virus even if their immune response isn't as strong. The study suggests that additional boosters might help and that regular monitoring of HIV treatment is necessary to ensure that both humoral (vaccine-related) and cellular immunity remains effective against the SARS-CoV-2 virus in people with weakened immune systems.

Abstract

The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.

Article URL: https://www.nature.com/articles/s41541-024-00972-3

Title

Biochemical rationale for transfusion of high titre COVID-19 convalescent plasma

🤖 Abstract

We developed an immunosorbent assay to measure how well donor antibodies bind to viruses that cause COVID-19 after receiving plasma from people who have recovered from the disease. We found two different affinities of these antibodies: 80% for IgG and about half for IgA. The binding strength was highest at a concentration of around 150 nanomoles per milliliter, which is higher than what's needed to be effective.

Abstract

We aimed to model binding of donor antibodies to virus that infects COVID-19 patients following transfusion of convalescent plasma (CCP). An immunosorbent assay was developed to determine apparent affinity (Kd, app). Antibody binding to virus was modelled using antibody concentration and estimations of viral load. Assay and model were validated using reference antibodies and clinical data of monoclonal antibody therapy. A single Kd, appor two resolvable Kd, appwere found for IgG in 11% or 89% of CCP donations, respectively. For IgA this was 50%-50%. Median IgG Kd, appwas 0.8nM and 3.6nM for IgA, ranging from 0.1-14.7nM and 0.2-156.0nM respectively. The median concentration of IgG was 44.0nM (range 8.4-269.0nM) and significantly higher than IgA at 2.0nM (range 0.4-11.4nM). The model suggested that a double CCP transfusion (i.e. 500 mL) allows for > 80% binding of antibody to virus provided Kd, appwas < 1nM and concentration > 150nM. In our cohort from the pre-vaccination era, 4% of donations fulfilled these criteria. Low and mid-range viral loads are found early post exposure, suggesting that convalescent plasma will be most effective then. This study provides a biochemical rationale for selecting high affinity and high antibody concentration CCP transfused early in the disease course.

Article URL: https://www.nature.com/articles/s41598-024-75093-x

Title

Comparative analyses of post-infectious olfactory dysfunction between COVID-19 and non-COVID-19 cases

🤖 Abstract

Research identifies differences between people who develop olfactory dysfunction (OD) after a COVID-19 infection and those without it. Demographic and clinical characteristics of patients with PIOD are analyzed to compare their experiences. The study found that: * A higher proportion of COVID-19 cases were younger, more likely male, and had parosmia. * Initial olfactory function tests showed differences between the groups. * Treatment improved odor detection threshold but not identification in COVID-19-associated OD. * Non-COVID-19-associated OD had better initial results.

Abstract

To identify the differences between COVID-19-associated and non-COVID-19-associated olfactory dysfunction (OD), we analyzed demographic and clinical characteristics based on the causative virus (COVID versus non-COVID groups) in patients with post-infectious olfactory dysfunction (PIOD) who underwent the olfactory questionnaire and olfactory function test. Out of 169 patients with PIOD, 99 were diagnosed with COVID-19 (COVID group), while 70 were not (non-COVID group). The COVID group was younger and had a higher percentage of male patients as well as patients with parosmia than the non-COVID group. In the initial olfactory function tests, the TDI, discrimination and identification scores were significantly higher in the COVID group than in the non-COVID group. TDI scores were significantly increased in patients with PIOD after treatment, regardless of the group. The threshold score was significantly increased by 1.38 in the COVID group while the identification score was significantly increased by 2.67 in the non-COVID group. Patients with COVID-19-associated OD were younger in age, tended to be male, had a higher incidence of parosmia, and had better initial olfactory function test results compared to those with non-COVID-19-associated OD. Following treatment, odor detection threshold improved in the COVID group, whereas odor identification improved in the non-COVID group.

Article URL: https://www.nature.com/articles/s41598-024-74629-5

Title

Coronavirus envelope protein activates TMED10-mediated unconventional secretion of inflammatory factors

🤖 Abstract

Here's a simplified abstract: Coronavirus proteins can trigger a strong inflammatory response in the body. Scientists have identified a specific protein called the envelope (E) protein on some coronaviruses that is particularly effective at causing this inflammation. In contrast, other types of coronaviruses cause less severe reactions. They found that when these E proteins are present, they help to release chemicals into the body's cells that trigger more inflammation. Researchers also discovered a molecule called progesterone that can block this process and reduce inflammation in some animal studies. This discovery suggests that targeting the E protein could be an effective way to prevent severe coronavirus infections.

Abstract

The precise cellular mechanisms underlying heightened proinflammatory cytokine production during coronavirus infection remain incompletely understood. Here we identify the envelope (E) protein in severe coronaviruses (SARS-CoV-2, SARS, or MERS) as a potent inducer of interleukin-1 release, intensifying lung inflammation through the activation of TMED10-mediated unconventional protein secretion (UcPS). In contrast, the E protein of mild coronaviruses (229E, HKU1, or OC43) demonstrates a less pronounced effect. The E protein of severe coronaviruses contains an SS/DS motif, which is not present in milder strains and facilitates interaction with TMED10. This interaction enhances TMED10-oligomerization, facilitating UcPS cargo translocation into the ER-Golgi intermediate compartment (ERGIC)—a pivotal step in interleukin-1 UcPS. Progesterone analogues were identified as compounds inhibiting E-enhanced release of proinflammatory factors and lung inflammation in a Mouse Hepatitis Virus (MHV) infection model. These findings elucidate a molecular mechanism driving coronavirus-induced hyperinflammation, proposing the E-TMED10 interaction as a potential therapeutic target to counteract the adverse effects of coronavirus-induced inflammation.

Article URL: https://www.nature.com/articles/s41467-024-52818-0

Title

Long COVID at 3 and 6 months after covid-19 infection in Thailand

🤖 Abstract

The study found that a significant number of people who contracted COVID-19 continue to experience symptoms after four weeks. The prevalence of these symptoms varies by country and over time - they can occur as early as three months (36.2%) and up to six months (33.7%). Factors such as gender, disease severity, and whether the person was infected with a mild or severe case also influence when symptoms start and how long they last.

Abstract

“Long COVID”, which describes a diverse set of symptoms or conditions that persist or develop after four weeks from the onset of initial SARS-CoV-2 infection has been introduced. However, the true prevalence varies worldwide. This study aimed to determine the point prevalence and clinical characteristics of long COVID at three and six months after acute COVID-19 infection in Thailand. Methods All adult patients who were diagnosed with COVID-19 by positive nasopharyngeal RT-PCR for SARS-CoV-2 at Thammasat University Hospital between October and December 2021 were recruited and followed for long COVID symptoms by telephone interviews at 3 and 6 months after an acute infection. Among 1,400 eligible COVID-19 cases, interviews were complete for 1,129 and 932 individuals at 3 and 6 months, respectively. Of those, 431 and 314 reported at least one symptom consistent with long COVID. The point prevalence was 38.2% (95% confidence interval: 35.3–41.1%) and 33.7% (95% confidence interval: 30.7–36.7%) respectively. Female gender, disease severity, and symptomatic acute infection were identified as independent risk factors. Conclusion Based on the reported symptoms, long COVID is commonly observed either at 3 or 6 months in our study.

Article URL: https://www.nature.com/articles/s41598-024-75233-3

Title

Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome

🤖 Abstract

A study has been conducted to understand the relationship between COVID-19, biliary injury, and cholestasis in critically ill patients. Researchers analyzed data from 225 COVID-19 patients who were admitted to an ICU at a hospital in Austria. They found that nearly half (53%) of these patients developed cholestasis, which is indicated by an abnormal level of alkaline phosphatase. Cholestasis was associated with higher levels of inflammation and liver damage markers. Patients with cholestasis also had worse survival rates during the ICU stay and after six months. The study suggests that developing cholestasis in COVID-19 patients can be a negative prognostic marker, indicating a poorer outcome.

Abstract

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.

Article URL: https://www.nature.com/articles/s41598-024-73948-x

Title

Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines

🤖 Abstract

Seasonal flu epidemics affect a lot of people worldwide due to influenza viruses. Vaccines help prevent infection but need updating every year because they can change over time. Researchers created a new type of vaccine that can produce more effective and quicker results, using an existing technology from another vaccine called COVID-19 mRNA vaccine. This new vaccine is made up of tiny genetic material (RNA) that helps the body's immune system recognize and fight off certain flu viruses.

Abstract

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4+T cell responses, and HA-specific CD8+T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ+CD4+T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.

Article URL: https://www.nature.com/articles/s41541-024-00980-3

Title

Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

🤖 Abstract

Since 2019, a new virus called SARS-CoV-2 has caused multiple waves of illness and hospitalizations. The virus's spike protein plays a crucial role in entering cells, but its behavior changes depending on how it's shaped. Researchers have been studying the shape of this protein to understand how it interacts with receptors on cell surfaces. Using detailed computer models and biological samples, scientists found that when the spike protein is correctly shaped as expected, it can bind to a specific receptor called ACE2 more easily. However, they also observed that the virus's spike protein can change shape and interact with its host better when this binding process begins. These changes help prevent the virus from being stopped by antibodies that are designed to recognize and neutralize other forms of the virus. Understanding how these viral proteins work could lead to new treatments for COVID-19 and other illnesses caused by similar viruses.

Abstract

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the RBD in the down-conformation to facilitate the conformational shift to RBD-up remains unclear. Herein, we present the structures of the BA.2.86 and the JN.1 spike proteins bound to ACE2. Notably, we successfully observed the ACE2-bound down-RBD, indicating an intermediate structure before the RBD-up conformation. The wider and mobile angle of RBDs in the up-state provides space for ACE2 to interact with the down-RBD, facilitating the transition to the RBD-up state. The K356T, but not N354-linked glycan, contributes to both of infectivity and neutralizing-antibody evasion in BA.2.86. These structural insights the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization.

Article URL: https://www.nature.com/articles/s41467-024-52808-2

Title

COVID-19 mRNA booster vaccination induces robust antibody responses but few adverse events among SARS-CoV-2 naïve nursing home residents

🤖 Abstract

Residents in nursing homes face higher risks from COVID-19. We studied who got vaccinated with a COVID-19 mRNA vaccine and how their bodies reacted to it. Our study included 95 people who had never been infected with SARS-CoV-2 before, including 69 older adults. Nobody reported serious side effects like heart attacks or seizures. However, some of the less severe side effects were more common in nurses than doctors. We found that those who got vaccinated had stronger immune systems and fewer problems compared to people who didn't get vaccinated at all.

Abstract

Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with ‘any AE’ and ‘no AE’ among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities.

Article URL: https://www.nature.com/articles/s41598-024-73004-8

Title

Evidence for SARS-CoV-2 infected Golden Syrian hamsters (Mesocricetus auratus) reducing daily energy expenditure and body core temperature

🤖 Abstract

Here's a simplified abstract that a young person can understand: Golden Syrian hamsters are used to test how they react to infections with a coronavirus called SARS-CoV-2. To see what happens when these hamsters get infected, researchers studied their physical changes over time after infection. They looked at things like energy expenditure, water intake, weight, body temperature, and activity levels in both healthy and sick hamsters. The results showed that infected hamsters had less energy and water than non-infected ones, which could be a sign of problems with their internal organs.

Abstract

Golden Syrian hamsters (Mesocricetus auratus) are a well-established animal model for human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their susceptibility to SARS-CoV-2 infection, robust virus replication and pathological manifestations similar to human COVID-19 pneumonia. To investigate the physiological changes upon infection in this animal model, we explored the alterations in daily energy expenditure (DEE), water turnover, body mass, body temperature, and locomotor activity in non-infected and SARS-CoV-2 infected Golden Syrian hamsters for four days post SARS-CoV-2. DEE was measured using the doubly labelled water method, which allows for the accurate estimation of carbon dioxide production and, consequently, energy expenditure in animals. Additionally, we investigated total water intake (TWI), which comprises drinking water, preformed water in food, and metabolic water. Using intraperitoneally implanted data loggers, we also monitored body core temperature and locomotor activity in some of the animals. Here we provide evidence for infected hamsters exhibiting significantly lower DEE and TWI compared to non-infected animals. We also observed an increase in body weight in the non-infected animals, while infected animals experienced weight loss. Further, infected animals showed a significantly decreased body temperature, indicating a generally lowered metabolic rate.

Article URL: https://www.nature.com/articles/s41598-024-73765-2

Title

COVID-19 detection from exhaled breath

🤖 Abstract

A new method for detecting COVID-19 has been developed. This system uses a simple device that collects breath samples from the air, then analyzes them using advanced technology. The system is non-invasive and can identify people who have COVID-19 with high accuracy. An initial trial of 302 participants showed promising results, achieving similar accuracy to traditional methods for detecting COVID-19.

Abstract

The SARS-CoV-2 coronavirus emerged in 2019 causing a COVID-19 pandemic that resulted in 7 million deaths out of 770 million reported cases over the next 4 years. The global health emergency called for unprecedented efforts to monitor and reduce the rate of infection, pushing the study of new diagnostic methods. In this paper, we introduce a cheap, fast, and non-invasive COVID-19 detection system, which exploits only exhaled breath. Specifically, provided an air sample, the mass spectra in the 10–351 mass-to-charge range are measured using an original micro and nano-sampling device coupled with a high-precision spectrometer; then, the raw spectra are processed by custom software algorithms; the clean and augmented data are eventually classified using state-of-the-art machine-learning algorithms. An uncontrolled clinical trial was conducted between 2021 and 2022 on 302 subjects who were concerned about being infected, either due to exhibiting symptoms or having recently recovered from illness. Despite the simplicity of use, our system showed a performance comparable to the traditional polymerase-chain-reaction and antigen testing in identifying cases of COVID-19 (that is, 95% accuracy, 94% recall, 96% specificity, and 92%\(F_1\)-score). In light of these outcomes, we think that the proposed system holds the potential for substantial contributions to routine screenings and expedited responses during future epidemics, as it yields results comparable to state-of-the-art methods, providing them in a more rapid and less invasive manner.

Article URL: https://www.nature.com/articles/s41598-024-74104-1

Title

An adaptive weight ensemble approach to forecast influenza activity in an irregular seasonality context

🤖 Abstract

### Abstract Simplified Forecasting flu activity in places like Hong Kong is tricky because the flu doesn't always follow a normal pattern. We used different types of smart tools to predict how the flu will spread up to 8 weeks ahead. We looked at data from many years, starting from 1998. We made groups of simple and complex models together (ensemble), which all did better than just guessing there would be no flu. The best group reduced errors by 23% to 29%. Another special way we blended the tools worked even better, reducing mistakes by 52%, which was much better at predicting different types of flu patterns. We tested this again after a big flu season (post-COVID), and it still helped reduce mistakes. Our system lets us compare different models and pick the best one for forecasting flu in places where the flu doesn't always come when expected.

Abstract

Forecasting influenza activity in tropical and subtropical regions, such as Hong Kong, is challenging due to irregular seasonality and high variability. We develop a diverse set of statistical, machine learning, and deep learning approaches to forecast influenza activity in Hong Kong 0 to 8 weeks ahead, leveraging a unique multi-year surveillance record spanning 32 epidemics from 1998 to 2019. We consider a simple average ensemble (SAE) of the top two individual models, and develop an adaptive weight blending ensemble (AWBE) that dynamically updates model contribution. All models outperform the baseline constant incidence model, reducing the root mean square error (RMSE) by 23%–29% and weighted interval score (WIS) by 25%–31% for 8-week ahead forecasts. The SAE model performed similarly to individual models, while the AWBE model reduces RMSE by 52% and WIS by 53%, outperforming individual models for forecasts in different epidemic trends (growth, plateau, decline) and during both winter and summer seasons. Using the post-COVID data (2023–2024) as another test period, the AWBE model still reduces RMSE by 39% and WIS by 45%. Our framework contributes to comparing and benchmarking models in ensemble forecasts, enhancing evidence for synthesizing multiple models in disease forecasting for geographies with irregular influenza seasonality.

Article URL: https://www.nature.com/articles/s41467-024-52504-1

Title

Rational design based on multi-monomer simultaneous docking for epitope imprinting of SARS-CoV-2 spike protein

🤖 Abstract

Molecularly imprinted polymers (MIPs) are like designer plastic molecules that mimic how antibodies interact with antigens found in nature. These plastics can be used to catch viruses like the one causing COVID-19. Recently, scientists developed a new way to make these MIPs using computer simulations and experiments. They looked at a part of the virus called Spike protein to find the best places for their plastic molecules to attach. They tested many different combinations of building blocks until they found the ones that worked best. The results showed that the designer plastics could be very good at catching viruses, just like antibodies do in our bodies. This method can help make better plastics for catching other types of dangerous viruses too.

Abstract

Among biomimetic strategies shaping engineering designs, molecularly imprinted polymer (MIP) technology stands out, involving chemically synthesised receptors emulating natural antigen-antibody interactions. These versatile ‘designer polymers’ with remarkable stability and low cost, are pivotal forin vitrodiagnostics. Amid the recent global health crisis, we probed MIPs’ potential to capture SARS-CoV-2 virions. Large biotemplates complicate MIP design, influencing generated binding site specificity. To precisely structure recognition sites within polymers, we innovated an epitope imprinting method supplemented byin silicopolymerization component screening. A viral surface Spike protein informed epitope selection was targeted for MIP development. A novel multi-monomer docking approach (MMSD) was employed to simulate classical receptor-ligand interactions, mimicking binding reinforcement across multiple amino acids. Around 40 monomer combinations were docked to the epitope sequence and top performers experimentally validated via rapid fluorescence binding assays. Notably, high imprinting factor polymers correlated with MMSD predictions, promising rational MIP design applicable to diverse viral pathologies.

Article URL: https://www.nature.com/articles/s41598-024-73114-3

Title

Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19

🤖 Abstract

Monocytes can turn into special cells called alveolar macrophages in the lungs. These cells help fix injuries but sometimes cause more damage over time. Researchers looked at people who had trouble breathing after getting better from COVID-19. They found that when these special lung repair cells were more present or less helpful, it meant the person's lung problems were worse or didn't go away. This suggests these cells might not help fix lungs as well as they should.

Abstract

Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy.

Article URL: https://www.nature.com/articles/s41590-024-01975-x

Title

Pharmacodynamic, prognostic, and predictive biomarkers in severe and critical COVID-19 patients treated with sirukumab

🤖 Abstract

We studied certain chemicals in sick people's blood who had very bad cases of COVID-19 and were given a special antibody called sirukumab. We found that when these chemicals didn't change much after treatment, the patients got better faster. This is especially true for patients with the most severe form of COVID-19. So, if someone doesn't see changes in these chemicals while taking the medicine, they might benefit more from it. The study ID number is NCT04380961.

Abstract

We examined candidate biomarkers for efficacy outcomes in hospitalized COVID-19 patients who were treated with sirukumab, an IL-6 neutralizing antibody, in a randomized, double-blind, placebo-controlled, phase 2 trial. Between May 2020 and March 2021, 209 patients were randomized (sirukumab,n= 139; placebo,n= 70); 112 had critical COVID-19. Serum biomarkers were evaluated for the pharmacodynamic effect of sirukumab and for their potential prognostic and predictive effect on time to sustained clinical improvement up to Day 28, clinical improvement at Day 28, and mortality at Day 28. The absence of detectable IL-4 increase and smaller increases in CCL13 post-baseline were most significantly associated with better response to sirukumab (versus placebo) treatment for all clinical efficacy outcomes tested, especially in patients with critical COVID-19. These data suggest that patients with critical COVID-19 without detectable sirukumab-induced IL-4 levels are more likely to benefit from sirukumab treatment. ClinicalTrials.gov Identifier: NCT04380961.

Article URL: https://www.nature.com/articles/s41598-024-74196-9

Title

Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage

🤖 Abstract

The BA.2.86 variant, especially its subvariant JN.1, spread widely in the US during winter 2023-24, but didn't cause as many hospitalizations or deaths as previous waves of COVID-19 did. To understand why this happened, researchers looked at people who had caught these variants compared to others infected with related variants like XBB. They found that: - More people with BA.2.86 got vaccinated. - People with BA.2.86 also had more past infections with different COVID strains. - Less of these people ended up needing hospital care. The researchers think this might be because their immune systems didn't respond as strongly to the new variant, possibly due to prior vaccinations or previous infections. This means they were less likely to get very sick from BA.2.86 compared to other variants. Keeping an eye on how SARS-CoV-2 variants evolve and impact health will help doctors plan better responses in the future.

Abstract

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023–24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

Article URL: https://www.nature.com/articles/s41467-024-52668-w

Title

Deep learning-derived optimal aviation strategies to control pandemics

🤖 Abstract

The COVID-19 pandemic affected many countries worldwide, causing governments to create strict health rules to stop the spread of the virus. This led to economic problems too. To understand how airplanes played a role in spreading the virus, scientists created a new tool called DWSAGE. It's like a smart map that learns from daily changes in airplane flights around the world. Scientists used this tool to see which places with lots of airplane traffic might have spread more COVID-19. They found out Western Europe, the Middle East, and North America had high airplane traffic. Based on their findings, scientists suggested reducing airplane travel to help control the virus without stopping people from moving around much. Their work gives a powerful tool for studying future outbreaks and helps governments make better decisions about air travel rules.

Abstract

The COVID-19 pandemic affected countries across the globe, demanding drastic public health policies to mitigate the spread of infection, which led to economic crises as a collateral damage. In this work, we investigate the impact of human mobility, described via international commercial flights, on COVID-19 infection dynamics on a global scale. We developed a graph neural network (GNN)-based framework called Dynamic Weighted GraphSAGE (DWSAGE), which operates over spatiotemporal graphs and is well-suited for dynamically changing flight information updated daily. This architecture is designed to be structurally sensitive, capable of learning the relationships between edge features and node features. To gain insights into the influence of air traffic on infection spread, we conducted local sensitivity analysis on our model through perturbation experiments. Our analyses identified Western Europe, the Middle East, and North America as leading regions in fueling the pandemic due to the high volume of air traffic originating or transiting through these areas. We used these observations to propose air traffic reduction strategies that can significantly impact controlling the pandemic with minimal disruption to human mobility. Our work provides a robust deep learning-based tool to study global pandemics and is of key relevance to policymakers for making informed decisions regarding air traffic restrictions during future outbreaks.

Article URL: https://www.nature.com/articles/s41598-024-73639-7

Title

The impact of COVID-19 on the debate on open science: a qualitative analysis of published materials from the period of the pandemic

🤖 Abstract

This study looked at how people talked about open science during the pandemic. It found that many thought the pandemic showed why open science is important. Words like "stress test" or "revolution" were used to describe how the pandemic affected open science. People also believed open science helped fight the pandemic by giving clear information to everyone. But when talking, they mostly focused on sharing data and preprints (early versions of research papers), checking for mistakes in info, and stopping misinformation. They also started thinking about how open science can help make things fairer for all people. So, even though some old ideas kept coming up, the main topics were new ways to think about how science connects with society and makes it more equal for everyone.

Abstract

This study is an analysis of the international debate on open science that took place during the pandemic. It addresses the question, how did the COVID-19 pandemic impact the debate on open science? The study takes the form of a qualitative analysis of a large corpus of key articles, editorials, blogs and thought pieces about the impact of COVID on open science, published during the pandemic in English, German, Portuguese, and Spanish. The findings show that many authors believed that it was clear that the experience of the pandemic had illustrated or strengthened the case for open science, with language such as a “stress test”, “catalyst”, “revolution” or “tipping point” frequently used. It was commonly believed that open science had played a positive role in the response to the pandemic, creating a clear ‘line of sight’ between open science and societal benefits. Whilst the arguments about open science deployed in the debate were not substantially new, the focuses of debate changed in some key respects. There was much less attention given to business models for open access and critical perspectives on open science, but open data sharing, preprinting, information quality and misinformation became most prominent in debates. There were also moves to reframe open science conceptually, particularly in connecting science with society and addressing broader questions of equity.

Article URL: https://www.nature.com/articles/s41599-024-03804-w

Title

Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages

🤖 Abstract

The coronavirus keeps changing, making some medicines ineffective against new versions like Omicron. But scientists found two special antibodies that work well against these changes. One works by targeting part of the virus's spike protein that stays the same even when it mutates. The other targets a different part and can still stop older versions but not newer ones. Understanding how our bodies fight these changes could help make better medicines to treat COVID-19.

Abstract

The continuous emergence of SARS-CoV-2 variants of concern has rendered many therapeutic monoclonal antibodies (mAbs) ineffective. To date, there are no clinically authorized therapeutic antibodies effective against the recently circulating Omicron sub-lineages BA.2.86 and JN.1. Here, we report the isolation of broad and potent neutralizing human mAbs (HuMabs) from a healthcare worker infected with SARS-CoV-2 early in the pandemic. These include a genetically unique HuMab, named K501SP6, which can neutralize different Omicron sub-lineages, including BQ.1, XBB.1, BA.2.86 and JN.1, by targeting a highly conserved epitope on the N terminal domain, as well as an RBD-specific HuMab (K501SP3) with high potency towards earlier circulating variants that was escaped by the more recent Omicron sub-lineages through spike F486 and E484 substitutions. Characterizing SARS-CoV-2 spike-specific HuMabs, including broadly reactive non-RBD-specific HuMabs, can give insight into the immune mechanisms involved in neutralization and immune evasion, which can be a valuable addition to already existing SARS-CoV-2 therapies.

Article URL: https://www.nature.com/articles/s42003-024-06951-7

Title

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

🤖 Abstract

### ABSTRACT SUGGESTED FOR YOUNG PERSONS Coronavirus can change how your brain works even if you didn't get very sick. Researchers looked at young people who had milder cases and found changes in certain parts of their brains months later. They noticed problems with some areas like the hippocampus (helps remember things) and amygdala (helps process emotions). These changes can affect how well they do tasks that involve remembering places, even if these kids were fine at first. The findings might help doctors understand long-term effects on the brain from COVID-19 infections.

Abstract

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta(i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta(i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdeltasignificantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdeltabetween groups (p= 0.041). The reduced ECdeltain the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Article URL: https://www.nature.com/articles/s41398-024-03108-2

Title

Impact of the COVID-19 pandemic on patients with peripheral arterial disease in China: a multicenter cross-sectional study

🤖 Abstract

This study looked at how having a disease called peripheral arterial disease (PAD) affected people who were hospitalized during different times: before and after the pandemic started. Before the pandemic, 762 patients with PAD were treated, on average aged 72 years. After the pandemic, 478 patients were treated, on average aged 65 years. During the pandemic, more patients had problems like very bad legs (CLTI), foot infections, and damage to blood vessels in their legs. Their leg condition got worse too. Treating these patients was harder during the pandemic, which made it hard for them to get better. The study also found that having certain issues, like diabetes or kidney problems, could make things worse. These people had more serious health problems after being treated during the pandemic. Overall, doctors still tried their best to help patients with severe PAD even though there were many challenges. The study shows it's important to keep treating and checking on these patients closely.

Abstract

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Article URL: https://www.nature.com/articles/s41598-024-71247-z

Title

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome

🤖 Abstract

This study looked at the body's response to a sickness called MIS-C in children who had COVID-19. They measured certain chemicals (called cytokines) in kids' blood before and after treatment with special medicines. They found three main groups of these chemicals: 1. The first group had mainly bad chemicals that make inflammation worse. 2. The second group had some good chemicals plus some bad ones, which stayed around a bit longer. 3. The third group saw its levels go up later on, with more kinds of bad chemicals. These changes show how the body fights off sickness and helps kids get better. It starts by making lots of inflammatory chemicals to fight infections, then it makes more specific memory cells so it can keep fighting if needed in the future.

Abstract

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients’ sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7–10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7–10 days of hospitalization and therapy, including IL-1α, IL-1β, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

Article URL: https://www.nature.com/articles/s41598-024-73956-x

Title

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection

🤖 Abstract

This article talks about a new way to make vaccines against norovirus, which is a stomach bug that spreads easily. Scientists used special material called mRNA-LNP to create a vaccine for two types of norovirus. This vaccine helped the body's immune system produce strong antibodies that can fight off these viruses. The antibodies stopped the virus from infecting tiny models of the human gut, showing this vaccine works well in tests. This means scientists have proof their method is effective and could make better vaccines against norovirus in the future.

Abstract

Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

Article URL: https://www.nature.com/articles/s41541-024-00976-z

Title

Surface protein distribution in Group B Streptococcus isolates from South Africa and identifying vaccine targets through in silico analysis

🤖 Abstract

Group B Strep (GBS) is a germ that can cause serious illnesses like pneumonia, meningitis, and sepsis in babies under 3 months old. It can also lead to stillbirths and early births in mommies who are pregnant. For older adults or people with weak immune systems, GBS causes different diseases. Right now, there's no vaccine that works against GBS. By looking at the genetic makeup of GBS, scientists found some important parts they think could be used to make a vaccine. They did this by testing lots of GBS samples from babies and mommies in South Africa. They looked for which parts of GBS are similar between the sick ones (that's what "invasive" means) and those that live on but don't cause problems yet ("colonizing"). Out of 89 possible vaccine candidates, they found 10 very common parts. Nine of these were special proteins called "computational inferred proteins," which is a fancy way of saying the scientists figured out their identity by looking at genetic data. One part was a surface protein that helps GBS stick to cells. They also looked at how likely each part is to trigger an immune response, which is important for vaccines. The nine special parts they found were more likely to do this than the surface protein. This suggests these could be good targets for making a vaccine against GBS.

Abstract

Group BStreptococcus(GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets.

Article URL: https://www.nature.com/articles/s41598-024-73175-4

Title

Effects of age and gender on immunogenicity and reactogenicity of SpikoGen recombinant spike protein vaccine: a post-hoc analysis

🤖 Abstract

### ABSTRACT Simplified The SpikoGen COVID-19 vaccine uses part of the virus's spike protein. It was tested in people of different ages and genders to see how well it works. After one dose, older people had fewer side effects like tiredness and headache. Men also felt fewer side effects than women after each dose. The vaccine didn't affect neutralizing antibodies differently between men and women or age groups. The vaccine is good at getting into the body's immune system but doesn’t cause many bad reactions. This shows that even if you don't feel too sick from a vaccine, it’s still working well to protect against COVID-19. SpikoGen seems like a promising way to make vaccines.

Abstract

SpikoGen® COVID-19 vaccine is based on the spike protein extracellular domain of the ancestral Wuhan-Hu-1 strain modified by removal of the furin cleavage site and addition of stabilising mutations expressed as a recombinant protein in insect cells. It is formulated with Advax-CpG55.2™ adjuvant to ensure optimal immunogenicity. In this study, data from several SpikoGen® clinical trials was retrospectively analysed to assess for any effect of gender or age on seroconversion, neutralizing antibody levels or the incidence of adverse events. Following the 1st dose, older age was associated with a reduced rate of fatigue (RR 0.97, p < 0.001), headache (RR 0.98, p = 0.034) and myalgia (RR 0.97, p=0.016), following the 2nd dose, the rate of fatigue (RR 0.98, p = 0.017) but following the 3rd dose no effect of age on adverse events was evident. Similarly, following the 1st dose, men reported a 19% lower incidence of fatigue, 36% lower incidence of headache and 28% lower incidence of myalgia when compared to women. Interestingly, there was no relationship between age or gender and serum neutralizing antibody levels, although after each vaccine dose there was a consistent trend to women having a higher seroconversion rate. There was no correlation between neutralizing antibody levels and adverse events. Unlike what is seen with mRNA vaccines, reactogenicity trended lower after each subsequent SpikoGen® dose. Overall, SpikoGen® exhibited positive immunogenicity and low reactogenicity, indicating that a low incidence of adverse events does not equate to poor immunogenicity. SpikoGen® remains a promising protein-based vaccine platform for COVID-19 protection.

Article URL: https://www.nature.com/articles/s41598-024-67945-3

Title

Deep learning for discriminating non-trivial conformational changes in molecular dynamics simulations of SARS-CoV-2 spike-ACE2

🤖 Abstract

This study uses advanced computer models to analyze how a part of the SARS-CoV-2 virus protein interacts with another protein in the human body. They converted these complex data into simpler maps for easier understanding, then used AI to guess which changes in the virus might make it more contagious or harder to fight off. They found that some changes to this part of the virus can make it stick better to its target and also makes it less noticeable to the immune system. This helps them predict how different types of mutations might affect the virus's ability to spread and avoid being detected by the body’s defenses. The AI also showed a good match between what they predicted and actual changes in how well the virus sticks, which is important for understanding its behavior. They discovered that one particular part of the protein moves around more than usual when there are these mutations, suggesting it might be key to evading the immune response. Overall, this method can help scientists quickly find new strains of the virus that could spread better or hide from our bodies' defenses. This is useful for making new treatments and vaccines faster.

Abstract

Molecular dynamics (MD) simulations produce a substantial volume of high-dimensional data, and traditional methods for analyzing these data pose significant computational demands. Advances in MD simulation analysis combined with deep learning-based approaches have led to the understanding of specific structural changes observed in MD trajectories, including those induced by mutations. In this study, we model the trajectories resulting from MD simulations of the SARS-CoV-2 spike protein-ACE2, specifically the receptor-binding domain (RBD), as interresidue distance maps, and use deep convolutional neural networks to predict the functional impact of point mutations, related to the virus’s infectivity and immunogenicity. Our model was successful in predicting mutant types that increase the affinity of the S protein for human receptors and reduce its immunogenicity, both based on MD trajectories (precision = 0.718; recall = 0.800;\(\hbox {F}_1\)= 0.757; MCC = 0.488; AUC = 0.800) and their centroids. In an additional analysis, we also obtained a strong positive Pearson’s correlation coefficient equal to 0.776, indicating a significant relationship between the average sigmoid probability for the MD trajectories and binding free energy (BFE) changes. Furthermore, we obtained a coefficient of determination of 0.602. Our 2D-RMSD analysis also corroborated predictions for more infectious and immune-evading mutants and revealed fluctuating regions within the receptor-binding motif (RBM), especially in the\(\beta _{1}^{\prime }/\beta _{2}^{\prime }-C\)loop. This region presented a significant standard deviation for mutations that enable SARS-CoV-2 to evade the immune response, with RMSD values of 5Å in the simulation. This methodology offers an efficient alternative to identify potential strains of SARS-CoV-2, which may be potentially linked to more infectious and immune-evading mutations. Using clustering and deep learning techniques, our approach leverages information from the ensemble of MD trajectories to recognize a broad spectrum of multiple conformational patterns characteristic of mutant types. This represents a strategic advantage in identifying emerging variants, bypassing the need for long MD simulations. Furthermore, the present work tends to contribute substantially to the field of computational biology and virology, particularly to accelerate the design and optimization of new therapeutic agents and vaccines, offering a proactive stance against the constantly evolving threat of COVID-19 and potential future pandemics.

Article URL: https://www.nature.com/articles/s41598-024-72842-w

Title

Oneyear longitudinal study on biomarkers of blood–brain barrier permeability in COVID-19 patients

🤖 Abstract

This study looked at how a virus called COVID-19 affects the brain. They found that after getting sick, the blood-brain barrier (which keeps things from going into the brain) was more leaky for a little while. This led to some extra chemicals in the blood coming from cells in the brain. These extra chemicals are like astrocyte-derived extracellular vesicles and S100B. They checked if these extra chemicals were related to symptoms that kept lasting for months after getting sick. But they didn't find any link between the levels of these chemicals and long-term problems people still had even after a year. The study found that after about 4 months, these extra chemicals peaked (were at their highest), but by the end of the year, they were back to normal. The main thing is that while there are signs of brain changes during an infection, those don't seem to cause long-term health issues. More research is needed to understand why some people have problems for so long after having COVID-19.

Abstract

The pathophysiology behind neurological and cognitive sequelae of COVID-19 may be related to dysfunction of the blood-brain barrier (BBB) and previous research indicate transient neuronal injury and glial activation. The aim of this study was to investigate if COVID-19 is related to increased BBB permeability by analyzing leakage of biomarkers such as astrocyte-derived extracellular vesicles (EVs) and S100B. We also investigated whether levels of these biomarkers correlated with self-reported symptoms that persisted > 2 months. The samples in this 1-year follow-up study came from an ongoing longitudinal study of unvaccinated patients hospitalized for COVID-19 at Danderyd University Hospital, Stockholm, Sweden, between April and June 2020. Blood samples were collected at baseline and 4, 8, and 12 months after hospitalization. Information on self-reported clinical symptoms was collected at follow-up visits. A total of 102 patients were enrolled, and 47 completed all follow-up measurements. Peak levels of both biomarkers were observed at 4 months in the subset of 55 patients who were measured at this timepoint. At 12 months, the biomarkers had returned to baseline levels. The biomarkers were not correlated with any of the long-term self-reported symptoms. COVID-19 is associated with transient increased BBB permeability, shown by elevated levels of astrocyte biomarkers in plasma. However, these levels return to baseline 12 months post-infection and do not correlate with long-term symptoms. Further research is needed to unravel the underlying mechanisms causing long-term symptoms in COVID-19 patients.

Article URL: https://www.nature.com/articles/s41598-024-73321-y

Title

Modeling the burden of long COVID in California with quality adjusted life-years (QALYS)

🤖 Abstract

This study looked at a sickness called "long COVID" that some people get even after they had very little or no symptoms from the original coronavirus illness. They used data on all confirmed cases in California over several years. They divided people into different age groups and measured how many life-years of quality were lost due to long COVID. The study found that more older adults (65+) lost these life years compared to younger ones, but surprisingly, younger adults (18-49) also had a significant loss when you consider all the mild and moderate symptoms. The researchers think their estimates might be lower than what really happened because they didn't account for everyone who got long COVID. They found that how many people developed long COVID and which symptoms were severe or mild affected their results the most. Overall, this study helps us understand more about the impact of "long COVID" in different age groups and how it compares to regular cases like hospitalizations.

Abstract

Individuals infected with SARS-CoV-2 may develop post-acute sequelae of COVID-19 (“long COVID”) even after asymptomatic or mild acute illness. Including time varying COVID symptom severity can provide more informative burden estimates for public health response. Using a compartmental model driven by confirmed cases, this study estimated long COVID burden by age group (0–4, 5–17, 18–49, 50–64, 65+) in California as measured by the cumulative and severity-specific proportion of quality-adjusted life years (QALYs) lost. Long COVID symptoms were grouped into severe, moderate, and mild categories based on estimates from the Global Burden of Disease study, and symptoms were assumed to decrease in severity in the model before full recovery. All 10,945,079 confirmed COVID-19 cases reported to the California Department of Public Health between March 1, 2020, and December 31, 2022, were included in the analysis. Most estimated long COVID-specific QALYs [59,514 (range: 10,372–180,257)] lost in California were concentrated in adults 18–49 (31,592; 53.1%). Relative to other age groups, older adults (65+) lost proportionally more QALYs from severe long COVID (1,366/6,984; 20%). Due to changing case ascertainment over time, this analysis might underestimate the actual total burden. In global sensitivity analysis, estimates of QALYs lost were most sensitive to the proportion of individuals that developed long COVID and proportion of cases with each initial level of long COVID symptom severity (mild/moderate/severe). Models like this analysis can help translate observable metrics such as cases and hospitalizations into quantitative estimates of long COVID burden that are currently difficult to directly measure. Unlike the observed relationship between age and incident severe outcomes for COVID-19, this study points to the potential cumulative impact of mild long COVID symptoms in younger individuals.

Article URL: https://www.nature.com/articles/s41598-024-73160-x

Title

Developing aCoccidioides posadasiiand SARS-CoV-2 Co-infection Model in the K18-hACE2 Transgenic Mouse

🤖 Abstract

### ABSTRACT SIMPLIFIED Scientists wanted to see how getting sick twice at once affects you. They did this by putting two different sicknesses into mice—like a mock infection. One sickness was caused by the virus that causes COVID-19, and the other was from a fungus called Valley Fever. They found that if they gave both sicknesses to the mice one after another, the mice got much sicker and lived less time than those who only had one sickness. This happened more with certain types of coronavirus (like Delta or Omicron) and sometimes depended on when each sickness came first. The scientists also noticed differences in how the immune system reacted to both sicknesses. The ones that caught the fungus first were healthier, but still got sick from the virus. Those that caught the virus first had a harder time recovering from Valley Fever. These findings suggest people who live where Valley Fever is common might have a worse experience if they get COVID-19 there too.

Abstract

BackgroundEarly reports showed that patients with COVID-19 had recrudescence of previously resolved coccidioidomycosis (Valley fever, VF), and there were indications that coinfection had more severe outcomes. We therefore investigated serial infection ofCoccidioides posadasiiand SARS-CoV-2 in a K18-hACE2 mouse model to assess disease outcomes.MethodsIn our model, we challenged K18-hACE2 mice sequentially with a sub-lethal dose of SARS-CoV-2 and 24 hours later with low virulence strain ofCoccidioides posadasii, and vice versa, compared to mice that only received a single infection challenge. We performed survival and pathogenesis mouse studies as well as looked at the systemic immune response differences between treatment groups.ResultsHere we show that co-infected groups have a more severe disease progression as well as a decrease in survival. Importantly, results differ depending on the SARS-CoV-2 variant (WA-1, Delta, or Omicron) and infection timing (SARS-CoV-2 first,C. posadasiisecond or vice versa). We find that groups that are infected with the virus first had a decrease in survival, increased morbidity and weight loss, increased fungal and viral burdens, differences in immune responses, and the amount and size of fungal spherules. We also find that groups coinfected withC. posadasiifirst have a decrease fungal burden and inflammatory responses.ConclusionsThis is the first in vivo model investigation of a coinfection of SARS-CoV-2 andCoccidioides. Because of the potential for increased severity of disease in a coinfection, we suggest populations that live in areas of high coccidioidomycosis endemicity may experience higher incidence of complicated disease progression with COVID-19.

Article URL: https://www.nature.com/articles/s43856-024-00610-y

Title

Systemic cytokines related to memory function 6–9 months and 12–15 months after SARS-CoV-2 infection

🤖 Abstract

This study looked at how cytokines, which are chemicals made by the body during infections, might affect people's memories months after they had COVID. They found that levels of one cytokine called IL-1β were linked to remembering words better about 6-9 months later. Another cytokine, IL-6, seemed to affect memory around a year after infection. This suggests how sick someone was during the early stages of their COVID could impact their ability to remember things over time.

Abstract

Cognitive symptoms persisting beyond the acute phase of COVID-19 infection are commonly described for up to 2 years after infection. The relationship between cognitive performance, in particular episodic memory processes observed chronically after infection, and cytokine levels in the acute phase of COVID-19 has not yet been identified in humans. To determine whether the levels of cytokines IL1β, IL-6 and TNFα secreted in the acute phase of SARS-CoV-2 infection are associated and predict verbal and visuospatial episodic memory performance in humans 6 to 9 months and 12 to 15 months post-infection. The associations and predictive value of the concentration of cytokines measured in acute phase (IL-1β, IL-6, TNFα) from plasma samples ofN= 33 hospitalized COVID-19 patients (mean age 61 years, 39–78, 65% in intensive care) in relation to their verbal and visuospatial episodic memory performance measured at 6–9 months and 12–15 months post-infection were analyzed. To do this, we used Spearman correlations and generalised linear mixed models. IL-1β levels were associated with verbal episodic memory total recall scores 6–9 months post-infection. At 12–15 months post-infection IL-6 predicted verbal episodic memory score. This study demonstrated that the severity of inflammatory reaction at acute phase of SARS-CoV-2 infection predicts verbal episodic memory performance in the long-term post-infection.

Article URL: https://www.nature.com/articles/s41598-024-72421-z

Title

Post-COVID-19 condition symptoms among emergency department patients tested for SARS-CoV-2 infection

🤖 Abstract

This study found that many people who went to the hospital with emergency symptoms didn't have COVID-19, but some still had problems like coughing or trouble breathing. Even when doctors tested negative for COVID-19, almost one-third of those patients said they were having Post-COVID issues three months later. The problem is, it's hard to know if these are really from the coronavirus or just other illnesses. So doctors think we need better tests now to figure out what causes these symptoms so people can get proper treatment sooner.

Abstract

Symptoms of the Post-COVID-19 Condition are often non-specific making it a challenge to distinguish them from symptoms due to other medical conditions. In this study, we compare the proportion of emergency department patients who developed symptoms consistent with the World Health Organization’s Post-COVID-19 Condition clinical case definition between those who tested positive for Severe Acute Respiratory Syndrome Coronavirus-2 infection and time-matched patients who tested negative. Our results show that over one-third of emergency department patients with a proven acute infection meet Post-COVID-19 Condition criteria 3 months post-index visit. However, one in five test-negative patients who claim never having been infected also report symptoms consistent with Post-COVID-19 Condition highlighting the lack of specificity of the clinical case definition. Testing for SARS-CoV-2 during the acute phase of a suspected infection should continue until specific biomarkers of Post-COVID-19 Condition become available for diagnosis and treatment.

Article URL: https://www.nature.com/articles/s41467-024-52404-4

Title

Determination of key hub genes in Leishmaniasis as potential factors in diagnosis and treatment based on a bioinformatics study

🤖 Abstract

Leishmaniasis is a disease caused by parasites that are carried by infected sandflies. Researchers looked at data from patients with leishmaniasis on their skin wounds and compared it to healthy people. They used special methods to find genes that were more active or less active in the sick people. They found 407 genes that behaved differently between those with leishmaniasis and others. These genes are involved in immune responses, inflammation, and pathways related to fighting infections. The study also identified seven important genes (called hub genes) that help control these different gene activities. One of these genes, UBD, plays a role in how cells break down other molecules called ubiquitin. Another hub gene, UBD, is connected with several microRNAs, which are tiny molecules that can control gene activity. These findings could help doctors diagnose leishmaniasis earlier and develop new treatments or vaccines against the disease.

Abstract

Leishmaniasis is an infectious disease caused by protozoan parasites from different species of leishmania. The disease is transmitted by female sandflies that carry these parasites. In this study, datasets on leishmaniasis published in the GEO database were analyzed and summarized. The analysis in all three datasets (GSE43880, GSE55664, and GSE63931) used in this study has been performed on the skin wounds of patients infected with a clinical form of leishmania (Leishmania braziliensis), and biopsies have been taken from them. To identify differentially expressed genes (DEGs) between leishmaniasis patients and controls, the robust rank aggregation (RRA) procedure was applied. We performed gene functional annotation and protein-protein interaction (PPI) network analysis to demonstrate the putative functionalities of the DEGs. The study utilized Molecular Complex Detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to detect molecular complexes within the protein-protein interaction (PPI) network and conduct analyses on the identified functional modules. The CytoHubba plugin’s results were paired with RRA analysis to determine the hub genes. Finally, the interaction between miRNAs and hub genes was predicted. Based on the RRA integrated analysis, 407 DEGs were identified (263 up-regulated genes and 144 down-regulated genes). The top three modules were listed after creating the PPI network via the MCODE plug. Seven hub genes were found using the CytoHubba app and RRA: CXCL10, GBP1, GNLY, GZMA, GZMB, NKG7, and UBD. According to our enrichment analysis, these functional modules were primarily associated with immune pathways, cytokine activity/signaling pathways, and inflammation pathways. However, a UBD hub gene is interestingly involved in the ubiquitination pathways of pathogenesis. The mirNet database predicted the hub gene’s interaction with miRNAs, and results revealed that several miRNAs, including mir-146a-5p, crucial in fighting pathogenesis. The key hub genes discovered in this work may be considered as potential biomarkers in diagnosis, development of agonists/antagonist, novel vaccine design, and will greatly contribute to clinical studies in the future.

Article URL: https://www.nature.com/articles/s41598-024-73779-w

Title

Clinical presentations, systemic inflammation response and ANDC scores in hospitalized patients with COVID-19

🤖 Abstract

The study found that people with anosmia (loss of smell) or ageusia (loss of taste) are often diagnosed with COVID-19, especially with the alpha variant. They looked at 231 hospitalized COVID-19 patients in Taiwan and noticed some differences between those who had these symptoms and those who didn't. They found that younger people with anosmia/ageusia were usually healthier overall and less sick compared to others without these issues. Women also tended to have milder cases than men, though they both had similar smells and taste loss. The study showed that certain blood tests called NLRs and PLRs helped predict how long patients would stay in the hospital. The ANDC score is another tool that can estimate this length based on symptoms like coughing and fever. Overall, the research suggests that people with anosmia/ageusia might have less serious COVID-19 and a lower body inflammation response, especially if they are younger women. This score could help doctors predict how sick someone will get from the disease and how long they'll need to stay in the hospital.

Abstract

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (allp< 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (allp< 0.01), and between PLR and ESR and ferritin levels (p< 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (allp< 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients.

Article URL: https://www.nature.com/articles/s41598-024-73001-x

Title

SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+memory T cells exert immediate effector functions with enhanced IFN-γ production

🤖 Abstract

The study found that after getting vaccinated against COVID-19, some people still get infected (called breakthrough infections). In their noses, there are special immune cells called T cells that recognize the virus and try to fight it. These T cells can stay in the nose for a long time—up to a year—and they respond quickly when they see pieces of the virus again. The type of T cell that does this is identified as CD49a+. These T cells help by making chemicals called IFN-γ, which signals other immune cells to attack the virus. They also stay in their resting homes (tissue-resident marker) in the nose even after a long time without seeing the virus again.

Abstract

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+T cells. We detect multimer+CD8+T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+T cells–particularly the CD49a+subset–exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+T cells confirms the enhanced effector function of the CD49a+subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.

Article URL: https://www.nature.com/articles/s41467-024-52689-5

Title

Correlating COVID-19 severity with biomarker profiles and patient prognosis

🤖 Abstract

The study looked at how different things can affect how sick people get from the coronavirus and its long-term effects. They studied 226 people to see what makes some recover faster than others. Age, lower education, being of a certain race, overweight, having issues with blood clotting genes, heart or lung problems, diabetes, and other factors were found to make someone sicker. The study also saw that six months later, some people had less of certain things in their blood like FVIII, VWF, and DD. Some people had joint pain, muscle aches, trouble breathing, and swelling in their legs if they had diabetes or lung problems during recovery. People who kept having high levels of DD after getting better were more likely to feel breathless and get heartburn. Women were found to have leg swelling longer than men, and those with higher FVIII levels for a while also got swollen legs. Exercise helped prevent leg swelling. The study thinks blood vessels might be one reason why people are sicker from the virus or its long-term effects.

Abstract

COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001),MTHFRgene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.

Article URL: https://www.nature.com/articles/s41598-024-71951-w

Title

Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates

🤖 Abstract

The SARS-CoV-2 virus keeps changing, so scientists had to update the vaccines they give people. They chose new parts of the virus to fight based on lab tests. But sometimes it took too long to make these updated vaccines before the virus changed again. Now, researchers want to know if these updates help our immune system better fight off newer versions of the virus. They looked at data showing how well different vaccine parts worked against recent and older viruses. They found that using the new, updated parts in a booster dose helped build stronger antibodies compared to old vaccines. This means people might get more protection even if the virus changed while they were waiting for the update. This information helps doctors decide when to give updated doses of vaccines.

Abstract

The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine was no longer well-matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variants containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95% CI: 1.07–1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the rollout of future booster vaccination programmes.

Article URL: https://www.nature.com/articles/s41467-024-52194-9

Title

SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination

🤖 Abstract

Simplified abstract: MRNA vaccines against COVID-19 are good at stopping serious illness. But months later, people's body doesn't have many protection antibodies anymore. We looked inside people’s bones where antibodies are made to find out why. We found that even though some special antibody-making cells were still around, the main place these cells live (long-lived plasma cells) was mostly empty for COVID-19 antibodies. This might explain why after a while, people's body doesn't have enough protection against COVID-19 anymore. So basically, mRNA vaccines make good antibodies, but they run out quickly because there aren’t many of the main antibody-making cells left in bones.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly even though SARS-CoV-2-specific plasma cells can be found in the bone marrow (BM). Here, to explore this paradox, we enrolled 19 healthy adults at 2.5–33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. The ratios of non-LLPC:LLPC for influenza, tetanus and SARS-CoV-2 were 0.61, 0.44 and 29.07, respectively. In five patients with known PCR-proven history of recent infection and vaccination, SARS-CoV-2-specific ASCs were mostly absent from the LLPCs. We show similar results with measurement for secreted antibodies from BM ASC culture supernatant. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within 3–6 months after vaccination, were associated with IgG non-LLPCs. In all, our studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.

Article URL: https://www.nature.com/articles/s41591-024-03278-y

Title

A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models

🤖 Abstract

The new coronavirus (SARS-CoV-2) can't enter some types of lung cells even when it should be able to. Researchers found that this might be because these cells are already stressed, leading to the release of DNA from their mitochondria (a part inside cells). This causes the cGAS-STING pathway and other immune responses to get activated without being needed, stopping the virus from growing. By changing how these pathways work or using medicine to stop them, researchers were able to make the lung cells allow the virus to grow better. They also found that when they removed parts of the body's defense system (like cGAS-STING) in some lung cell samples, more coronavirus could grow there and cause less immune reactions. In summary, the stress inside certain lung cells seems to be stopping the coronavirus from growing properly, even if it’s supposed to enter them. How much this happens depends on how many of these special parts (like ACE2) are present in those cells.

Abstract

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway in productively infected cells. Pharmacological inhibition of STING in primary airway cells enhances SARS-CoV-2 replication and reduces virus-induced innate immune activation. Together, our study highlights that tonic activation of the cGAS-STING and IFN pathways can impact SARS-CoV-2 cellular tropism in a manner dependent on ACE2 expression levels.

Article URL: https://www.nature.com/articles/s41467-024-52803-7

Title

Altered functional brain connectivity, efficiency, and information flow associated with brain fog after mild to moderate COVID-19 infection

🤖 Abstract

The COVID-19 virus makes it harder for people to think clearly. We tested 49 adults, 25 who had been sick with COVID and 24 who hadn’t. The group that had COVID did worse on thinking tests. Their brains also showed less connection between different parts compared to the other group. Less brain connections mean it’s harder to process information efficiently. This could be a way for the brain to keep working but feel like it's foggy or fuzzy.

Abstract

COVID-19 is associated with increased risk for cognitive decline but very little is known regarding the neural mechanisms of this risk. We enrolled 49 adults (55% female, mean age = 30.7 ± 8.7), 25 with and 24 without a history of COVID-19 infection. We administered standardized tests of cognitive function and acquired brain connectivity data using MRI. The COVID-19 group demonstrated significantly lower cognitive function (W = 475, p < 0.001, effect size r = 0.58) and lower functional connectivity in multiple brain regions (mean t = 3.47 ±0.36, p = 0.03, corrected, effect size d = 0.92 to 1.5). Hypo-connectivity of these regions was inversely correlated with subjective cognitive function and directly correlated with fatigue (p < 0.05, corrected). These regions demonstrated significantly reduced local efficiency (p < 0.026, corrected) and altered effective connectivity (p < 0.001, corrected). COVID-19 may have a widespread effect on the functional connectome characterized by lower functional connectivity and altered patterns of information processing efficiency and effective information flow. This may serve as an adaptation to the pathology of SARS-CoV-2 wherein the brain can continue functioning at near expected objective levels, but patients experience lowered efficiency as brain fog.

Article URL: https://www.nature.com/articles/s41598-024-73311-0

Title

Impact of six-month COVID-19 travel moratorium onPlasmodium falciparumprevalence on Bioko Island, Equatorial Guinea

🤖 Abstract

The spread of malaria on Bioko Island is partly caused by people bringing the disease from other places. Scientists wanted to see how much this importation affects local cases. They used a six-month period when people weren't allowed to travel in and out as a test. Before and after this time, they checked if more people had malaria where many visitors come from. This showed that having visitors increases the chances of getting malaria. So stopping visitors could help reduce the number of malaria cases on the island.

Abstract

Importation of malaria infections is a suspected driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. Quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and complexity of designing a randomized trial. We leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to malaria prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compare the change in prevalence between areas of low historical travel to those with high historical travel. Here, we report that in the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 9% higher than observed, highlighting the importance of control measures that target imported infections.

Article URL: https://www.nature.com/articles/s41467-024-52638-2

Title

Key considerations for digital decentralised clinical trials from a feasibility study assessing pacing interventions for long COVID

🤖 Abstract

Long COVID is a condition that causes lots of problems like tiredness, trouble breathing, and brain fog. Many people who get Long COVID feel very sick and it's hard for doctors to find good treatments. Doctors need tools to test new ways to help people with Long COVID, but they don't have many. We made an online system where patients can join different groups doing different experiments at home. It helped us see if certain methods work better. We learned that getting people to join these studies is really hard, and some people pretend to be in the study when they're not. Also, many people stop joining before we finish all our tests. We found ways to solve some of these problems so doctors can do more effective online studies for Long COVID.

Abstract

Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management. We co-produced a mixed methods feasibility study to evaluate a multi-arm digital decentralised clinical trial (DCT) platform to assess non-pharmacological interventions for Long COVID, using pacing interventions as an exemplar. The study demonstrated that the platform was able to successfully e-consent participants, randomise them into one of four intervention arms, capture baseline data, and capture outcomes relevant to a health economic evaluation. The study also highlighted several challenges, including difficulties with recruitment, imposter participants, and high attrition rates. We highlight how these challenges can potentially be mitigated to make a fully powered DCT more feasible.

Article URL: https://www.nature.com/articles/s41598-024-61827-4

Title

Clinical and neuroimaging features in neurological Wilson’s disease with claustrum lesions

🤖 Abstract

Our study looked at how often patients with a rare brain condition called Wilson's disease have problems in an area of their brain called the claustrum. Early studies said this could happen anywhere from 1.8% to 75%. We wanted to find out more about these cases, like what symptoms they had and why it might be happening. In our study, we looked at MRI scans of 668 people with Wilson's disease. Out of the 443 who had issues shown on their brain scan, only 3 had bright claustrum signs seen on images. These signs were: - Appeared in both sides of the brain - Not isolated to just one part - Usually showed up only when people had very bad symptoms The bright claustrum sign might be a marker that inflammation is happening in the brain. The area was also hyperintense, meaning it appeared brighter on scans. So basically, we found that problems with this brain area are not common but usually appear in people who have really severe symptoms of Wilson's disease.

Abstract

According to early research, the incidence of claustrum lesions in patients with neurological Wilson’s disease (WD) was inconsistent, ranging from 1.8 to 75% on magnetic resonance imaging (MRI). Our study aims to explore the incidence, clinical presentation features, iconography features, and possible pathological mechanisms in WD patients with claustrum lesions on magnetic resonance imaging (MRI), to characterize the clinical, and brain imaging findings and possible pathological mechanisms in the patients with WD. Retrospective cases meeting the inclusion criteria were studied for analyzing MRI characteristics and associated physicochemical examination data in neurological WD patients with claustrum lesions. 443 (66.3%) with brain MRI abnormalities were screened from 668 WD patients. The three (0.7%) patients with the claustrum lesions characteristics on MRI images were: (a) “bright claustrum” in T2-weighted and FLAIR sequences, (b) bilateral symmetrical, (c) non-isolated lesions, (d) occurred only in severe neurological manifestations. The claustrum lesions are not common in neurological WD and mainly appear in cases with severe neurological symptoms. On MRI, the “bright claustrum” signs may be a radiographic marker of neuroinflammation, the features of the lesions showed bilateral symmetry, and hyperintensity signals on T2-weighted, FLAIR, and DWI.

Article URL: https://www.nature.com/articles/s41598-024-73475-9

Title

A novel isothermal whole genome sequencing approach for Monkeypox Virus

🤖 Abstract

Monkeypox virus causes a disease similar to chickenpox. Since May 2022, there have been more cases of people catching the virus from each other outside places where it's usually found. Scientists use something called Whole Genome Sequencing (WGS) to track how the virus changes over time during outbreaks or for watching many diseases that could affect people. There are different ways to do this sequencing, like using big machines or special chemicals. The new method uses a DNA polymerase enzyme called Phi29 and a technique called multiple displacement amplification (MDA). This allows them to get almost all the virus's genetic material without needing lots of steps. The scientists tested their new method with different types of samples - some from people who got sick, and other kinds too. They found out that it can work well using just 6 special pieces of DNA that act as starting points (primers). Their new method is good for keeping track of how the virus changes during outbreaks or to watch for it in places where we might not know about cases yet. It works even without fancy equipment, so any lab could use it.

Abstract

Monkeypox virus (MPXV) is the zoonotic agent responsible for mpox, an often-self-limiting pox-like disease. Since May 2022, an outbreak characterized by increased human-to-human transmission was detected outside the endemic regions. Whole genome sequencing (WGS) has been successfully used to keep track of viral evolution during outbreaks or for surveillance of multiple pathogens of public health significance. Current WGS protocols for MPXV are either based on metagenomic sequencing or tiled-PCR amplification. The latter allows multiplexing due to the efficient enrichment of the viral DNA, however, mutations or the presence of different clades can negatively influence genome coverage yield. Here, we present the establishment of a novel isothermal WGS method for MPXV based on Phi29 DNA polymerase-based multiple displacement amplification (MDA) properties making use of only 6 primers. This approach yielded from 88% up to 100% genome coverage using either alkaline denatured extracted DNA or clinical material as starting material, with the highest coverage generated by clinical material. We demonstrate that this novel isothermal WGS protocol is suitable for monitoring viral evolution during MPXV outbreaks and surveillance in any conventional laboratory setting.

Article URL: https://www.nature.com/articles/s41598-024-73613-3

Title

Mpox infection of stromal cells and macrophages of macaque with endometriosis

🤖 Abstract

The mpox outbreak in 2022-2023 was a new health problem that showed mpox can be spread through sex, though it mostly affected men who have sex with other men (MSM). Women are also at risk, especially during pregnancy. We studied some monkeys to see how they got infected. We found that mpox didn't just live in their skin - it was also inside the vagina and uterus of the monkeys. The study showed mpox could grow in special tissue called endometriosis. This is a condition where tissue like what grows in your uterus but is found elsewhere, usually on other organs like the ovaries. We learned that mpox likes to live in certain types of cells - specifically ones that help protect against infections and some of the cells inside the reproductive system. The study also suggested women with this condition might be more at risk for bad things happening if they get mpox. In general, this research shows us what happens when a disease like mpox affects the genital area. The monkeys were used because they're similar to humans in many ways and can help understand how diseases work.

Abstract

The mpox outbreak of 2022–2023 represented a new global health challenge and recognition of mpox as a sexually transmitted disease. The majority of cases were reported in men who have sex with men (MSM), but women are also susceptible, especially during pregnancy. We evaluated the reproductive tracts of a subset of macaques from a large rechallenge study of mpox infection with virus from the 2022 outbreak and identified intraabdominal mpox replication associated with endometriosis. Mpox virus (MPXV) was found not only in skin, but in the cervix, the uterus, and periovarian endometriotic lesions of the affected macaque. Mpox replication preferentially targeted vimentin-positive poorly differentiated endometriotic stromal tissue and infiltrating macrophages in the reproductive tract. Mpox tropism for stromal cells and macrophages has broad implications for mpox pathogenesis and associated clinical syndromes. In addition, women with endometriosis may be at heightened risk for adverse outcomes associated with mpox infection. The rhesus macaque provides rare insight into this disease and the potential complications of mpox infection in the context of genitourinary tract disease.

Article URL: https://www.nature.com/articles/s41598-024-73012-8

Title

A colorimetric reverse-transcription loop-mediated isothermal amplification method targeting the L452R mutation to detect the Delta variant of SARS-CoV-2

🤖 Abstract

Here's a simplified version of the abstract: A new coronavirus called SARS-CoV-2 has spread quickly around the world, causing problems for people and economies. A variant of this virus, known as Delta, is still widespread and can make COVID-19 vaccines less effective. To control the spread of the virus, scientists need to be able to detect it quickly. This study developed a new test that can specifically identify the Delta variant of SARS-CoV-2. The test uses a color-changing reaction to show whether someone has the virus or not. When tested with 126 real samples, the test was highly accurate and sensitive, making it a useful tool for tracking COVID-19 and developing strategies to control its spread in the future.

Abstract

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered global difficulties for both individuals and economies, with new variants continuing to emerge. The Delta variant of SARS-CoV-2 remains most prevalent worldwide, and it affects the efficacy of coronavirus disease 2019 (COVID-19) vaccination. Expedited testing to detect the Delta variant of SARS-CoV-2 and monitor viral transmission is necessary. This study aimed to develop and evaluate a colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) technique targeting the L452R mutation in the S gene for the specific detection of the Delta variant. In the test, positivity was indicated as a color change from purple to yellow. The assay’s 95% limit of detection was 57 copies per reaction for the L452R (U1355G)-specific standard plasmid. Using 126 clinical samples, our assay displayed 100% specificity, 97.06% sensitivity, and 98.41% accuracy in identifying the Delta variant of SARS-CoV-2 compared to real-time RT-PCR. To our knowledge, this is the first colorimetric RT-LAMP assay that can differentiate the Delta variant from its generic SARS-CoV-2, enabling it as an approach for studying COVID-19 demography and facilitating proper effective control measure establishment to fight against the reemerging variants of SARS-CoV-2 in the future.

Article URL: https://www.nature.com/articles/s41598-024-72417-9

Title

Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children

🤖 Abstract

This abstract is about studying how the body's immune system reacts differently when kids get very sick from various illnesses, like coronavirus or bacterial infections. They looked at blood samples from 74 kids with a condition called MIS-C (which happens after they had COVID), 30 with bacterial infections, 16 with viral infections, and 8 with Kawasaki disease. They found that in most cases, the body's neutrophils (a type of white blood cell) were overreacting or dying too quickly. They also noticed that T cells from kids with MIS-C and bacterial infections didn't work as well as they should. For viral infections like those from viruses other than SARS-CoV-2, their immune system showed less response to interferons, which are important for fighting off infections. This finding could help doctors figure out better ways to treat very sick children who have these illnesses.

Abstract

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Article URL: https://www.nature.com/articles/s41467-024-52246-0

Title

Low-frequency CD8+T cells induced by SIGN-R1+macrophage-targeted vaccine confer SARS-CoV-2 clearance in mice

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 vaccine needs two types of help from our immune system: special cells called T cells that can recognize and attack the virus, and antibodies that neutralize it. Our previous research showed that using a special delivery system called pullulan nanogel (PNG) could make these T cells stronger. We found out that PNG works by binding to a specific receptor on certain immune cells in our lymph nodes. In this study, we tested if using PNG with a part of the COVID-19 virus's spike protein as the vaccine could help protect against infection. In mice with COVID-19-like symptoms, we saw that the vaccine decreased the viral load and helped them survive longer. We also found out that even low-frequency T cells that responded quickly to the virus were important for clearing the virus. Overall, our study suggests that targeting specific immune cells in the lymph nodes can help make vaccines more effective by inducing strong T cell responses.

Abstract

Vaccine-induced T cells and neutralizing antibodies are essential for protection against SARS-CoV-2. Previously, we demonstrated that an antigen delivery system, pullulan nanogel (PNG), delivers vaccine antigen to lymph node medullary macrophages and thereby enhances the induction of specific CD8+T cells. In this study, we revealed that medullary macrophage-selective delivery by PNG depends on its binding to a C-type lectin SIGN-R1. In a K18-hACE2 mouse model of SARS-CoV-2 infection, vaccination with a PNG-encapsulated receptor-binding domain of spike protein decreased the viral load and prolonged the survival in the CD8+T cell- and B cell-dependent manners. T cell receptor repertoire analysis revealed that although the vaccine induced T cells at various frequencies, low-frequency specific T cells mainly promoted virus clearance. Thus, the induction of specific CD8+T cells that respond quickly to viral infection, even at low frequencies, is important for vaccine efficacy and can be achieved by SIGN-R1+medullary macrophage-targeted antigen delivery.

Article URL: https://www.nature.com/articles/s41541-024-00961-6

Title

UPLC-PDA factorial design assisted method for simultaneous determination of oseltamivir, dexamethasone, and remdesivir in human plasma

🤖 Abstract

A new way of testing medicine levels in blood using UPLC (a fast and precise lab technique) has been created. This method can measure three medicines at once: oseltamivir phosphate, remdesivir, dexamethasone, and a special standard called daclatasvir dihydrochloride. The medicines are put into the system one by one using tiny needles, and then separated on a special column that uses a mixture of methanol (a clear liquid) and ammonium acetate solution to sort them out based on their colors at different wavelengths. It takes just 5 minutes to do all this! The method was tested for accuracy and reliability according to international guidelines. Environmental Impact Scores, Green Assessment of Processes in Analysis, and Acceptability and Goodness-Instrument Rating (Eco-score, GAPI, and AGREE) showed that it is a good and environmentally friendly way to measure these medicines. This means it's useful and won't harm the environment.

Abstract

A green and simple UPLC method was developed and optimized, adopting a factorial design for simultaneous determination of oseltamivir phosphate and remdesivir with dexamethasone as a co-administered drug in human plasma and using daclatasvir dihydrochloride as an internal standard within 5 min. The separation was established on UPLC column BEH C181.7 μm (2.1\(\times \)100.0 mm) connected to UPLC pre-column BEH 1.7 μm (2.1\(\times \)5.0 mm) at 50 °C with an injection volume of 10 μL. The photodiode array detector (PDA) was set at three wavelengths of 220, 315, and 245 nm for oseltamivir phosphate, the internal standard, and both dexamethasone and remdesivir, respectively. The mobile phase consisted of methanol and ammonium acetate solution (40 mM) adjusted to pH 4 in a ratio of 61.5:38.5 (v/v) with a flow rate of 0.25 mL min−1. The calibration curves were linear over 500.0–5000.0 ng mL−1for oseltamivir phosphate, over 10.0–500.0 ng mL−1and 500.0–5000.0 ng mL−1for dexamethasone, and over 20.0–500 ng mL−1and 500.0–5000.0 ng mL−1for remdesivir. The Gibbs free energy and Van't Hoff plots were used to investigate the effect of column oven temperatures on retention times. Fluoride-EDTA anticoagulant showed inhibition activity on the esterase enzyme in plasma. The proposed method was validated according to the M10 ICH, FDA, and EMA’s bioanalytical guidelines. According to Eco-score, GAPI, and AGREE criteria, the proposed method was considered acceptable green.

Article URL: https://www.nature.com/articles/s41598-024-71413-3

Title

Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Scientists are trying to find new ways to stop COVID-19 from spreading. They've discovered that a protein called ACTN4 plays a crucial role in this process. When ACTN4 is reduced, it makes it harder for COVID-19 to multiply inside cells. Researchers also found two substances, YS-49 and demethyl-coclaurine, that can block COVID-19 infection. These substances work by targeting the protein that helps COVID-19 replicate. This study shows how important ACTN4 is in stopping COVID-19 from spreading and reveals new potential candidates for developing medicines to fight against the virus.

Abstract

The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level onACTN4(Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Article URL: https://www.nature.com/articles/s41392-024-01956-4

Title

The comparison of pathogenicity among SARS-CoV-2 variants in domestic cats

🤖 Abstract

Here's a simplified version of the abstract: Scientists found that a type of coronavirus called SARS-CoV-2 can infect domestic cats and even wild animals. They wanted to know if cats play a role in spreading this virus, so they did experiments on cats to see how well it spreads and how their bodies react. The results showed that cats are very susceptible to the SARS-CoV-2 virus and can spread it for up to 7 days after being infected. However, one type of the virus, called Omicron, didn't spread as well in cat tissues and caused less severe symptoms. The study also found that cats' bodies produced antibodies to fight off the virus. This suggests that while cats might be able to catch SARS-CoV-2, they're not very good at spreading it around, especially with the Omicron variant.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.

Article URL: https://www.nature.com/articles/s41598-024-71791-8

Title

Oral SARS-CoV-2 host responses predict the early COVID-19 disease course

🤖 Abstract

Here's a simplified version of the abstract: Researchers studied people who had COVID-19 to see how it affects their bodies, especially in their mouths and throats. They collected saliva and blood samples from 45 people and looked for signs of the virus and how their immune system responded. They found that most people with COVID-19 had the virus in their saliva and throat wash for up to 4 weeks after getting sick. Some people even showed signs of the virus in their saliva when they didn't have symptoms anymore. The researchers also discovered that people who were severely ill with COVID-19 tended to have more antibodies (which fight off infections) in their blood and saliva, especially in the early stages of the illness. They found that some people's immune system responded differently based on their sex, with women having higher levels of certain antibodies in their saliva. The study suggests that the virus can replicate (multiply) in the mouth and throat for a while after symptoms go away, which may be important for understanding how COVID-19 is transmitted to others. The researchers also found evidence that some people's immune system may "confuse" the virus with other proteins in their body, which could affect how well they fight off the infection. Overall, this study provides new insights into how COVID-19 affects the body and may help us understand more about the disease and how to prevent it from spreading.

Abstract

Oral fluids provide ready detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses. This study sought to evaluate relationships between oral virus, oral and systemic anti-SARS-CoV-2-specific antibodies, and symptoms. Oral fluids (saliva/throat wash (saliva/TW)) and serum were collected from asymptomatic and symptomatic, nasopharyngeal (NP) SARS-CoV-2 RT-qPCR+ human participants (n = 45). SARS-CoV-2 RT-qPCR and N-antigen detection by immunoblot and lateral flow assay (LFA) were performed. RT-qPCR for subgenomic RNA (sgRNA) was sequence confirmed. SARS-CoV-2-anti-S protein RBD LFA and ELISA assessed IgM and IgG responses. Structural analysis identified host salivary molecules analogous to SARS-CoV-2-N-antigen. At time of enrollment (baseline, BL), LFA-detected N-antigen in 86% of TW and was immunoblot-confirmed. However, only 3/17 were saliva/TW qPCR+ . Sixty percent of saliva and 83% of TW demonstrated persistent N-antigen at 4 weeks. N-antigen LFA signal in three anti-spike sero-negative participants suggested potential cross-detection of 4 structurally analogous salivary RNA binding proteins (alignment 19–29aa, RMSD 1–1.5 Angstroms). At enrollment, symptomatic participants demonstrated replication-associated sgRNA junctions, were IgG+ (94%/100% in saliva/TW), and IgM+ (63%/54%). At 4 weeks, SARS-CoV-2 IgG (100%/83%) and IgM (80%/67%) persisted. Oral and serum IgG correlated 100% with NP+ PCR status. Cough and fatigue severity (p= 0.010 and 0.018 respectively), and presence of weakness, nausea, and composite upper respiratory symptoms (p= 0.037, 0.005, and 0.017, respectively) were negatively associated with saliva IgM but not TW or serum IgM. Throat wash IgM levels were higher in women compared to men, although the association did not reach statistical significance (median: 290 (female) versus 0.697,p= 0.056). Important to transmission and disease course, oral viral replication and persistence showed clear relationships with select symptoms and early oral IgM responses during early infection. N-antigen cross-reactivity may reflect mimicry of structurally analogous host proteins.

Article URL: https://www.nature.com/articles/s41598-024-67504-w

Title

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

🤖 Abstract

Here's a simplified version of the abstract: We studied how antiviral treatments affect the COVID-19 virus in people with weakened immune systems. Fifteen patients were given different treatments, including remdesivir and nirmatrelvir-ritonavir, to see if the virus developed resistance. The results showed that nine out of 15 patients had viruses with mutations that made them harder to treat. We isolated a COVID-19 virus from one patient that was resistant to two common antiviral medications: remdesivir and nirmatrelvir. This study is important because it shows that the virus can develop resistance to these treatments, even after prolonged use. The infected virus was also shown to be transmissible to other animals in a lab experiment.

Abstract

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n= 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n= 3) or therapeutic monoclonal antibodies (n= 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Article URL: https://www.nature.com/articles/s41467-024-51924-3

Title

Monitoring SARS-CoV-2 IgA, IgM and IgG antibodies in dried blood and saliva samples using antibody proximity extension assays (AbPEA)

🤖 Abstract

Here's a simplified version of the abstract: Scientists developed a new test that can detect if someone has antibodies against COVID-19 just by looking at a small blood or saliva sample on a paper disc. The test uses special molecules that bind to the antibodies and then helps create a tiny piece of DNA, which is measured using a machine. This makes it possible to quickly and easily check if people have been vaccinated or infected with COVID-19. The study showed that this new test works well for detecting antibodies in blood samples, but less effectively in saliva samples. However, the results still suggest that it's a useful tool for monitoring the body's response to vaccination.

Abstract

Using a modified proximity extension assay, total and immunoglobulin (Ig) class-specific anti-SARS-CoV-2 antibodies were sensitively and conveniently detected directly from ø1.2 mm discs cut from dried blood and saliva spots (DBS and DSS) without the need for elution. For total Ig detection, antigen probes were prepared by conjugating recombinant spike protein subunit 1 (S1-RBD) to a pair of oligonucleotides. To detect isotype-specific antibody reactivity, one antigen probe was replaced with oligonucleotide-conjugated antibodies specific for antibody isotypes. Binding of pairs of oligonucleotide-conjugated probes to antibodies in patient samples brings oligonucleotides in proximity. An added DNA polymerase uses a transient hybridization between the oligonucleotides to prime synthesis of a DNA strand, which serves as a DNA amplicon that is quantified by real-time PCR. The S1-RBD-specific IgG, IgM, and IgA antibodies in DBS samples collected over the course of a first and second vaccination exhibited kinetics consistent with previous reports. Both DBS and DSS collected from 42 individuals in the autumn of 2023 showed significant level of total S1-RBD antibodies with a correlation of R = 0.70. However, levels in DSS were generally 10 to 100-fold lower than in DBS. Anti-S1-RBD IgG and IgA in DSS demonstrated a correlation of R = 0.6.

Article URL: https://www.nature.com/articles/s41598-024-72453-5

Title

Deficiency ofTlr7andIrf7in mice increases the severity of COVID-19 through the reduced interferon production

🤖 Abstract

Here's a simplified version of the abstract: Researchers studied how a deficiency in a certain receptor (Tlr7) affects the severity of COVID-19 in mice. They found that when this receptor is missing, the body has trouble producing interferons (IFNs), which are important for fighting the virus. The study showed that without Tlr7 and another related protein called Irf7, the mice developed more severe symptoms, had higher levels of the virus in their lungs, and took longer to produce antibodies against COVID-19. This suggests that the activation of these receptors is crucial for developing a strong defense against the virus.

Abstract

Toll-like receptor 7 (Tlr7)deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. To address these questions, we utilizeTlr7andIrf7deficiency mice, single-cell RNA analysis together with bone marrow transplantation approaches. We demonstrate that at the early phase of infection, SARS-CoV-2 causes the upregulation ofTlr7,Irf7, and IFN pathways in the lungs of the infected mice. The deficiency ofTlr7andIrf7globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma levels in the circulation. The deficiency ofTlr7tends to cause the reduced production and nuclear translocation of interferon regulatory factor 7 (IRF7) in the lungs of the infected mice, indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen,Tlr7orIrf7deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7 leading to IFN production on the development of innate and adaptive immunity against COVID-19.

Article URL: https://www.nature.com/articles/s42003-024-06872-5

Title

Longitudinal proteome-wide antibody profiling in Marburg virus survivors identifies wing domain immunogen for vaccine design

🤖 Abstract

This study looked at how the body makes antibodies after getting sick from the Marburg virus over many years. They found that different types of antibodies form over time: 1. The body starts by making lots of IgM and IgA antibodies quickly. 2. Later, it switches to making more IgG antibodies, which last longer. The study also noticed: - Antibodies against parts of a protein called GP are strongest. - Some old antibody types like IgM and IgA get less common over time. - The body forms strong bonds with special Fc receptors that can interact with the virus. These findings suggest that even though many antibodies don't help stop the virus directly, they might still fight against it indirectly by binding to parts of these proteins. This could be useful for developing treatments and vaccines.

Abstract

Limited knowledge exists on the quality of polyclonal antibody responses generated following Marburg virus (MARV) infection and its evolution in survivors. In this study, we evaluate MARV proteome-wide antibody repertoire longitudinally in convalescent phase approximately every six months for five years following MARV infection in ten human survivors. Differential kinetics were observed for IgM vs IgG vs IgA epitope diversity, antibody binding, antibody affinity maturation and Fc-receptor interaction to MARV proteins. Durability of MARV-neutralizing antibodies is low in survivors. MARV infection induces a diverse epitope repertoire with predominance against GP, VP40, VP30 and VP24 that persisted up to 5 years post-exposure. However, the IgM and IgA repertoire declines over time. Within MARV-GP, IgG recognize antigenic sites predominantly in the amino-terminus, wing domain and GP2-heptad repeat. Interestingly, MARV infection generates robust durable FcɣRI, FcɣRIIA and FcɣRIIIA IgG-Fc receptor interactions. Immunization with immunodominant MARV epitopes reveals conserved wing region between GP1 and GP2, induces neutralizing antibodies against MARV. These findings demonstrate that MARV infection generates a diverse, long-lasting, non-neutralizing, IgG antibody repertoire that perturbs disease by FcɣR activity. This information, along with discovery of neutralizing immunogen in wing domain, could aid in development of effective therapeutics and vaccines against Marburg virus.

Article URL: https://www.nature.com/articles/s41467-024-51021-5

Title

How storage post sampling influences the stability of sebum when used for mass spectrometry metabolomics analysis?

🤖 Abstract

Sebum is a natural oil produced by skin glands. Recent studies found this oil can show signs of diseases like Parkinson's. Since getting sebum is easy and doesn't hurt, doctors might use it in tests. Researchers looked at how well they could test sebum over time and under different temperatures. They collected sebum from people, stored it for up to four weeks at room temperature or very cold (like in a freezer), and then tested it using two types of machines that break down the oil into tiny parts we can see. They didn't find any difference between how the samples looked when they were stored for different amounts of time or at different temperatures. But, some small groups of samples mixed up with others. This study shows sebum is good to use in tests and doesn’t need to be kept cold forever. This means people can collect their own oil from home without worrying too much about it spoiling before they send it to the lab.

Abstract

Sebum is a biofluid excreted by sebaceous glands in the skin. In recent years sebum has been shown to contain endogenous metabolites diagnostic of disease, with remarkable results for Parkinson’s Disease. Given that sebum sampling is facile and non-invasive, its potential for use in clinical biochemistry diagnostic assays should be explored including the parameters for standard operating procedures around collection, transport, and storage. To this aim we have here investigated the reproducibility of mass spectrometry data from sebum in relation to both storage temperature and length of storage. Sebum samples were collected from volunteers and stored for up to four weeks at a range of temperatures: ambient (circa17 °C), −20 °C and −80 °C. Established extraction protocols were employed and samples were analysed by two chromatographic mass spectrometry techniques and data investigated using PCA, PLS-DA and ANOVA. We cannot discriminate samples as a function of storage temperature or time stored in unsupervised analysis using data acquired via TD–GC–MS and LC–IM–MS, although the sampling of volatiles was susceptible to batch effects. This study indicates that the requirements for storage and transport of sebum samples that may be used in clinical assays are less stringent than for liquid samples and indicate that sebum is suitable for remote and at home sampling prior to analysis.

Article URL: https://www.nature.com/articles/s41598-024-71598-7

Title

Text mining method to unravel long COVID’s clinical condition in hospitalized patients

🤖 Abstract

Long COVID is when you feel sick for a really long time after you get an illness like the flu or coronavirus. This can happen even weeks or months later. It's hard to understand because different people have different symptoms, and doctors use different words to describe them. In this study, scientists used special computer tools to look at old medical records from a hospital in Brazil. They looked for patterns and similar terms that might represent the same condition. This helped them see what long COVID looks like across many patients. They also found tricky words (like those with extra parts or opposite meanings) that can be confusing. By using these new computer tools, they hope to better understand this long-lasting sickness so doctors can help more people who are sick from it. These tools could work in other hospitals too!

Abstract

Long COVID is characterized by persistent that extends symptoms beyond established timeframes. Its varied presentation across different populations and healthcare systems poses significant challenges in understanding its clinical manifestations and implications. In this study, we present a novel application of text mining technique to automatically extract unstructured data from a long COVID survey conducted at a prominent university hospital in São Paulo, Brazil. Our phonetic text clustering (PTC) method enables the exploration of unstructured Electronic Healthcare Records (EHR) data to unify different written forms of similar terms into a single phonemic representation. We used n-gram text analysis to detect compound words and negated terms in Portuguese-BR, focusing on medical conditions and symptoms related to long COVID. By leveraging text mining, we aim to contribute to a deeper understanding of this chronic condition and its implications for healthcare systems globally. The model developed in this study has the potential for scalability and applicability in other healthcare settings, thereby supporting broader research efforts and informing clinical decision-making for long COVID patients.

Article URL: https://www.nature.com/articles/s41419-024-07043-4

Title

Astodrimer sodium nasal spray forms a barrier to SARS-CoV-2 in vitro and preserves normal mucociliary function in human nasal epithelium

🤖 Abstract

Here's a simplified version of the abstract: COVID-19 can be very serious for some people, especially those with weakened immune systems. To protect against this and other respiratory infections, scientists are looking at ways to create sprays that can help block the virus from entering the body through the nose. A new nasal spray called Astodrimer Sodium (AS) was tested along with four other types of sprays. The AS spray showed promise in blocking the virus and not harming the delicate cells in the nose. It also didn't interfere with the natural mucus-clearing function of the nose. In contrast, some of the other sprays had limited ability to block the virus and even caused problems by slowing down or stopping the mucus-clearing process. The AS spray seems to be a safe and effective option for protecting against respiratory viruses in the nose.

Abstract

COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity.

Article URL: https://www.nature.com/articles/s41598-024-72262-w

Title

Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors

🤖 Abstract

Here's a simplified version of the abstract: Background: Some people who got infected with COVID-19 also take medicine for high blood sugar. We wanted to know if taking a specific type of diabetes medication called SGLT2 inhibitors helps prevent heart and kidney problems. Methods: We looked at medical records of over 100,000 veterans in the US who had COVID-19 and took diabetes medication between March 2020 and June 2023. Some took SGLT2 inhibitors while others took different types of diabetes medication. Results: Our study found that people taking SGLT2 inhibitors were less likely to have serious heart problems (such as a heart attack or stroke) and kidney issues (such as needing dialysis). They also had fewer hospitalizations, anemia, and acute kidney injury. These benefits were seen after about 1.5 years of follow-up. Conclusions: Taking SGLT2 inhibitors may help people with COVID-19 on diabetes medication avoid heart and kidney problems.

Abstract

BackgroundWhether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.MethodsWe used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)—a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)—a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR).ResultsOver a median follow up of 1.57 (IQR: 1.05–2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)).ConclusionsAmong people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.

Article URL: https://www.nature.com/articles/s43856-024-00599-4

Title

SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 virus is still difficult to treat, especially when it becomes very severe. Scientists are trying to understand how the virus works so they can find new ways to fight it. One part of the virus, called the E protein, has been shown to be important for its growth and survival inside a host cell. Researchers have discovered that this E protein can interact with other proteins in the cell that help regulate calcium levels. This interaction can affect how well these proteins work, which can lead to inflammation and make COVID-19 more severe. The study found that the E protein can bind to these regulatory proteins and change their shape, making them less effective at doing their job. This could be a key part of why the virus causes such strong immune responses in people. By understanding how this works, scientists may be able to find new ways to treat COVID-19 by targeting these interactions between the E protein and other cell proteins.

Abstract

The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca2+homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirm that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca2+reload. Structural modeling of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.

Article URL: https://www.nature.com/articles/s41598-024-71144-5

Title

Symptom burden, coagulopathy and heart disease after acute SARS-CoV-2 infection in primary practice

🤖 Abstract

Here's a simplified version of the abstract: Scientists conducted a study called SETANTA to investigate how COVID-19 affects people's hearts. They looked at patients who had recently had COVID-19 and wanted to see if they still had symptoms or heart problems. The study found that many participants (83%) still had symptoms like fatigue, headaches, etc. The researchers also used tests to check the patients' hearts for damage and found that some of them had abnormal results. For example, about 2% of participants had inflammation in their hearts, while about 17% had a problem with their heart's ability to pump blood. Another important finding was that many patients (32%) had high levels of a protein called von Willebrand factor antigen, which can indicate an increased risk of clotting. The study suggests that people who recently recovered from COVID-19 may be at higher risk for future health problems due to persistent symptoms and abnormal heart readings.

Abstract

SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study aimed to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and to correlate these results with biomarkers of immunological response and coagulation. SETANTA was a prospective, single-arm observational cross-sectional study condcuted in a primary practice setting, and prospectively registered with ClinicalTrials.gov (identifier: NCT04823182). Patients with recent COVID-19 infection (≥ 6 weeks and ≤ 12 months) were prospectively enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (CMR), which included left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, as well as relevant biomarkers testing immunological response and coagulopathy. 100 patients (n = 129 approached) were included, amongst which 64% were female. Mean age of the total cohort was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% of participants had at least one persistent symptom, while 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively, while left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients and Fibrinogen and D-Dimer levels were found to be elevated in 10.2% and 11.1% of patients, respectively. In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on CMR compared with prior reports of patients assessed in a hospital setting.Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021).

Article URL: https://www.nature.com/articles/s41598-024-71535-8

Title

Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial

🤖 Abstract

Here's a simplified version of the abstract: A study was done to see how well antibodies in the blood protect against COVID-19 after getting vaccinated. The research showed that people who have these antibodies are less likely to get sick with COVID-19. But since new variants of the virus have emerged, scientists wanted to know if these antibodies still work. The study found that even though many people already had antibodies from previous vaccinations or infections, the level of protection they offered was still strong. In fact, having higher levels of antibodies meant a lower chance of getting COVID-19. This research suggests that measuring antibody levels in the blood can still be a good way to see how well someone is protected against COVID-19, even after new variants have emerged.

Abstract

In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Article URL: https://www.nature.com/articles/s41467-024-52348-9

Title

Immunologic mediators profile in COVID-19 convalescence

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: A new coronavirus called SARS-CoV-2 caused a global pandemic in 2020. To understand how our bodies fight this virus, scientists studied people who had recovered from COVID-19. They took blood samples from these individuals and measured different markers in their blood to see what happened as they got better. The study found that most people developed antibodies (special proteins) against the virus after getting sick. Some of these antibodies lasted longer than others. The researchers also saw changes in the types of immune cells (like soldiers) in the blood over time. What's interesting is that our immune system starts with a "fighting" response to the virus, but as we get better, it shifts towards a "repair" response. This study highlights the importance of understanding how our immune system works, especially after we've gotten sick with something like COVID-19. Knowing this can help us develop better treatments and vaccines in the future. The bottom line is that our bodies are pretty amazing at fighting off viruses, but there's still a lot to learn about how they work!

Abstract

SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal–Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

Article URL: https://www.nature.com/articles/s41598-024-71419-x

Title

Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Scientists have created new vaccine ingredients called antigens to help fight against COVID-19 viruses that keep changing over time. They designed three new antigens (called T2_32, T2_35, and T2_36) that work well together to protect people from different types of COVID-19 variants. Tests on animals showed that these new antigens are very effective at creating a strong defense against the virus. When given as a vaccine, they even worked better than some existing vaccines. These findings suggest that using computer-designed modifications to create more powerful vaccines could be an important tool in fighting against COVID-19 and its evolving variants.

Abstract

Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.

Article URL: https://www.nature.com/articles/s41541-024-00950-9

Title

Chemosensory assessment and impact on quality of life in neurosensorial cluster of the post COVID 19 syndrome

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 pandemic showed that some people experience problems with their sense of smell and taste after getting infected. This study looked at how common this problem was, what might make it more likely, and how well people recovered. About 47% of patients in this study had these problems, which were more common in women and less common in older adults who got a special treatment called monoclonal antibodies. When researchers tested some patients' sense of smell and taste, they found that about two-thirds could smell things only slightly or not at all, while one-fourth couldn't taste things normally. This study showed that problems with smell and taste after COVID-19 can be quite complex and unpredictable. Understanding this better will help doctors develop treatments to prevent or fix these problems in the future.

Abstract

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training’s outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment.

Article URL: https://www.nature.com/articles/s41598-024-71475-3

Title

Use of high-resolution fluorescence in situ hybridization for fast and robust detection of SARS-CoV-2 RNAs

🤖 Abstract

Here's a simplified version of the abstract: Detecting COVID-19 quickly and accurately is crucial to stopping its spread. We developed a fast test that can detect the virus in just 3 hours, using a special technique called FISH (fluorescence in situ hybridization). This test works by using tiny probes to find and highlight the presence of the virus's genetic material (RNA) in cells. We tested this method on cell cultures and found it to be accurate and efficient. We also used it to detect COVID-19 in samples from patients, including those taken from the mouth and throat. The results were excellent, with the test being able to identify the presence of the virus quickly and accurately. This new method could significantly improve the accuracy and speed of COVID-19 detection, making it easier to control outbreaks and keep people safe.

Abstract

Early, rapid, and accurate diagnostic tests play critical roles not only in the identification/management of individuals infected by SARS-CoV-2, but also in fast and effective public health surveillance, containment, and response. Our aim has been to develop a fast and robust fluorescence in situ hybridization (FISH) detection method for detecting SARS-CoV-2 RNAs by using an HEK 293 T cell culture model. At various times after being transfected with SARS-CoV-2 E and N plasmids, HEK 293 T cells were fixed and then hybridized with ATTO-labeled short DNA probes (about 20 nt). At 4 h, 12 h, and 24 h after transfection, SARS-CoV-2 E and N mRNAs were clearly revealed as solid granular staining inside HEK 293 T cells at all time points. Hybridization time was also reduced to 1 h for faster detection, and the test was completed within 3 h with excellent results. In addition, we have successfully detected 3 mRNAs (E mRNA, N mRNA, and ORF1a (−) RNA) simultaneously inside the buccal cells of COVID-19 patients. Our high-resolution RNA FISH might significantly increase the accuracy and efficiency of SARS-CoV-2 detection, while significantly reducing test time. The method can be conducted on smears containing cells (e.g., from nasopharyngeal, oropharyngeal, or buccal swabs) or smears without cells (e.g., from sputum, saliva, or drinking water/wastewater) for detecting various types of RNA viruses and even DNA viruses at different timepoints of infection.

Article URL: https://www.nature.com/articles/s41598-024-70980-9

Title

Robust immune response to COVID-19 vaccination in the island population of Greenland

🤖 Abstract

Here's a simplified version of the abstract: In Greenland, the COVID-19 pandemic was relatively mild compared to other countries. One reason for this might be that many people in Greenland got vaccinated against COVID-19. To understand how well the vaccines worked, researchers looked at the immune system response of 430 adults who had received two doses of the vaccine. They measured the levels of antibodies (which help fight off viruses) in these people's blood and saliva over a period of up to 11 months after their second dose. The results showed that almost all participants (96% after two months, and 98% after 11 months) had enough antibodies to protect them from COVID-19. People who had previously been infected with COVID-19 even had higher levels of antibodies. In people over 60 years old, the vaccine response was slightly weaker. The researchers also found that all participants had a strong T-cell response (another part of the immune system) against COVID-19. These results suggest that the vaccines were very effective in protecting Greenlanders against COVID-19, and contributed to the mild impact of the pandemic in the country.

Abstract

BackgroundIn Greenland, the COVID-19 pandemic was characterised by a late onset of community transmission and a low impact on the healthcare system, hypothesised as being partly due to a high uptake of vaccinations. To underpin this description, we aimed to assess the SARS-CoV-2 immune response post-vaccination in a Greenlandic population.MethodsIn this observational cohort study, we included 430 adults in Greenland who had received a complete two-dose SARS-CoV-2 vaccination at enrolment. The total plasma SARS-CoV-2 spike glycoprotein Ig antibodies (S-Ab) induced by either the BNT162b2 or mRNA-1273 vaccine, was measured up to 11 months after the second vaccine dose. In addition, total salivary S-Abs were examined in 107 participants, and the T-cell response to the spike glycoprotein was assessed in 78 participants out of the entire study cohort.ResultsHere we demonstrate that two months after the second vaccine dose, 96% of participants have protective plasma S-Ab levels. By 11 months, 98% have protective levels, with prior SARS-CoV-2 infection particularly enhancing S-Ab levels by 37% (95% CI 25–51%). Among individuals aged 60 years and older, we observe a 21% (95% CI 7–33%) reduction in antibody response. Total salivary S-Ab levels are detectable in all participants and significantly correlate with plasma levels. Moreover, all participants exhibit a robust SARS-CoV-2-specific T-cell response 11 months post-primary vaccination.ConclusionsOur findings show that Greenlanders exhibit a robust and lasting immune response, both humoral and cellular, comparable to other population groups up to at least 11 months after the second vaccine dose. These results corroborate the hypothesis that vaccines contributed to the mild impact of the COVID-19 pandemic in the Greenlandic population.

Article URL: https://www.nature.com/articles/s43856-024-00602-y

Title

A Gaussia luciferase reporter assay for the evaluation of coronavirus Nsp5/3CLpro activity

🤖 Abstract

Human coronaviruses cause sickness in many people each year. Some types like MERS, SARS-CoV-1, and SARS-CoV-2 can be very serious. To help stop these viruses from spreading, scientists are looking for new medicines that can fight them. A drug called Paxlovid has already been used successfully to treat some of these illnesses by stopping a protein inside the virus called 3CLpro. But sometimes, if we use the same drug too much or for too long, the virus might start to get stronger and not work as well anymore. So researchers want to find more ways to fight these viruses. They created an easy-to-use test that can quickly tell them how strong a virus is and if medicines are working against it. This test uses parts of another protein found in our bodies (ACE2-Gal4) along with the 3CLpro from coronaviruses. When 3CLpro cuts this protein, it causes a light-producing chemical to be made. This new test can work on any coronavirus and can measure both how well medicine is stopping the virus and if the virus has become more powerful in some way. They tested the medicine Paxlovid using their test and found that it works against SARS-CoV-2 3CLpro. The test also helped them understand better how mutations (changes) in the 3CLpro protein can make it stronger or weaker, which is important for future research. Overall, this new test makes it easier to study coronavirus proteins and find new medicines.

Abstract

Human coronaviruses (hCoVs) infect millions of people every year. Among these, MERS, SARS-CoV-1, and SARS-CoV-2 caused significant morbidity and mortality and their emergence highlights the risk of possible future coronavirus outbreaks. Therefore, broadly-active anti-coronavirus drugs are needed. Pharmacological inhibition of the hCoV protease Nsp5 (3CLpro) is clinically beneficial as shown by the wide and effective use of Paxlovid (nirmatrelvir, ritonavir). However, further treatment options are required due to the risk of drug resistance. To facilitate the assessment of coronavirus protease function and its pharmacological inhibition, we developed an assay allowing rapid and reliable quantification of Nsp5 activity under biosafety level 1 conditions. It is based on an ACE2-Gal4 transcription factor fusion protein separated by a Nsp5 recognition site. Cleavage by Nsp5 releases the Gal4 transcription factor, which then induces the expression of Gaussia luciferase. Our assay is compatible with Nsp5 proteases from all hCoVs and allows simultaneous measurement of inhibitory and cytotoxic effects of the tested compounds. Proof-of-concept measurements confirmed that nirmatrelvir, GC376 and lopinavir inhibit SARS-CoV-2 Nsp5 function. Furthermore, the assay accurately predicted the impact of Nsp5 mutations on catalytic activity and inhibitor sensitivity. Overall, the reporter assay is suitable for evaluating viral protease activity.

Article URL: https://www.nature.com/articles/s41598-024-71305-6

Title

Influence of mRNA Covid-19 vaccine dosing interval on the risk of myocarditis

🤖 Abstract

Here's a simplified version of the abstract: A serious heart condition called myocarditis is more likely to happen after getting certain COVID-19 vaccines. The risk is highest after the second dose and lower with later booster doses. We studied over 7,000 cases of myocarditis in people aged 12 and up to see if there's a connection between how often you get vaccinated and the risk of this condition. Our results show that taking longer breaks between vaccine doses can decrease the risk by up to four times, especially for people under 50. This suggests that waiting at least six months before getting another booster shot might be a good idea.

Abstract

Myocarditis is the most salient serious adverse event following messenger RNA-based Covid-19 vaccines. The highest risk is observed after the second dose compared to the first, whereas the level of risk associated with more distant booster doses seems to lie in between. We aimed to assess the relation between dosing interval and the risk of myocarditis, for both the two-dose primary series and the third dose (first booster). This matched case-control study included 7911 cases of myocarditis aged 12 or more in a period where approximately 130 million vaccine doses were administered. Here we show that longer intervals between each consecutive dose, including booster, may decrease the occurrence of vaccine-associated myocarditis by up to a factor of 4, especially under age 50. These results suggest that a minimum 6-month interval might be required when scheduling additional booster vaccination.

Article URL: https://www.nature.com/articles/s41467-024-52038-6

Title

Impact of COVID-19 pandemic on ocular disease: KNHANES 2015–2021

🤖 Abstract

Here's a simplified version of the abstract: This study looked at how the COVID-19 pandemic affected eye diseases and changed people's risk factors in South Korea between 2015 and 2021. The researchers analyzed data from over 50,000 people and found that being infected with COVID-19 increased the risk of developing cataracts and age-related macular degeneration (a type of vision loss). They also found that other health conditions like high blood pressure, diabetes, and depression were linked to eye diseases too. However, having COVID-19 did not increase the risk of getting glaucoma (another type of eye disease). The study suggests that cataracts and age-related macular degeneration might be more affected by people's lifestyle and environment rather than just their genetic predisposition.

Abstract

The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015–2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.

Article URL: https://www.nature.com/articles/s41598-024-70767-y

Title

Broad protection and respiratory immunity of dual mRNA vaccination against SARS-CoV-2 variants

🤖 Abstract

Here's a simplified version of the abstract: Scientists have been working on vaccines to protect us from COVID-19. However, the virus has changed over time, making some vaccines less effective. Researchers developed a new type of vaccine that targets a specific part of the virus and tested it alone or combined with another vaccine in hamsters. The results showed that the new vaccine, when used alone or together with the other vaccine, was very good at protecting against certain types of COVID-19. Additionally, studies in mice found that this combination vaccine triggered an immune response specifically in the lungs, which is where COVID-19 typically infects us. These findings suggest that this new vaccine could be effective against various strains of COVID-19 and help prevent future outbreaks.

Abstract

While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.

Article URL: https://www.nature.com/articles/s41541-024-00957-2

Title

Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 pandemic is still a problem and some new versions of the virus (called BA.2.86 and JN.1) are spreading fast around the world. These viruses have many mutations that make it harder for our immune systems to fight them off. Scientists studied these new viruses and found out how they evade our antibodies, which are like superheroes that protect us from germs. They also looked at the structure of the virus and how it interacts with human cells. They discovered some important changes in the way these new viruses attach to human cells, making it harder for them to be stopped by our immune systems. This research helps us understand why these new viruses are spreading quickly and what we can do to stop them. It's like having a map of where the virus is evolving and how it's adapting to avoid being caught by our bodies' defenses.

Abstract

The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

Article URL: https://www.nature.com/articles/s41467-024-51973-8

Title

Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates

🤖 Abstract

This study looked at different ways to give a vaccine for a virus that causes the flu in animals (SARS-CoV-2). They compared two methods: putting the vaccine directly into someone's arm, or giving it through their nose or mouth. The team found that when they gave the vaccine through the nose and mouth, it worked better. The vaccine helped protect against the virus not just in the throat but also deep inside the lungs. This method also made the immune system create antibodies (special proteins) that can help stop the virus from spreading. In contrast, giving the vaccine by putting it into someone's arm only protected the lower parts of their airways. The study suggests that giving a vaccine through the nose or mouth might be better because: 1. It stops the virus in both the throat and lungs. 2. It makes antibodies that can stop other people from catching the virus too. 3. It makes certain immune cells that help fight off the virus. So, this research shows how giving a vaccine through the nose or mouth could better protect against SARS-CoV-2 and prevent it from spreading to others.

Abstract

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

Article URL: https://www.nature.com/articles/s41590-024-01951-5

Title

Acute-phase proteins as indicators of disease severity and mortality in COVID-19 patients

🤖 Abstract

The study looked at how certain chemicals called acute-phase proteins (APPs) affect how sick people get from COVID-19. They measured these chemicals in 96 people with COVID-19, along with some healthy people for comparison. They found that: - The levels of APPs change depending on how sick someone is from the disease and if they're getting enough oxygen. - In very severe cases, where there's a lot of inflammation (called a cytokine storm), these chemicals can go up or down a lot. - There are some APPs that don't usually get tested. The researchers found that two of them - procalcitonin and transferrin - help doctors tell if someone is going to survive their COVID-19. They also noticed that measuring how sick people were using something called the MEWS scale didn't always match with another system used by doctors (National Institutes of Health). The researchers concluded that: - Not all APPs change based on how bad a person's disease gets. - Only two out of many tested APPs can help predict if someone will survive their COVID-19. - Among the new ones they looked at, transferrin is the only one that seems to really matter in predicting who will get better or worse from COVID-19.

Abstract

The aim of the study was to conduct of relationship of acute-phase proteins (APPs) with the severity of COVID-19 defined by National Institutes of Health and according to the criteria of MEWS scale, with the presence of a cytokine storm, oxygen therapy and patient survival. We enrolled 96 patients with COVID-19 and 30 healthy people. The samples were taken on the day of admission and after 9 days on average. Not only commonly used APPs such as CRP, procalcitonin and ferritin and also rarely assayed proteins such as transferrin, haptoglobin, α1-acid glycoprotein and α1-antitrypsin, were tested in the study. The levels of APPs depends on the severity of COVID-19 disease, on the presence of cytokine storm and used oxygen therapy. The greatest APPs changes occurred in the most advanced form of the disease, with the presence of a cytokine storm and the most intense oxygen therapy. The results obtained from MEWS scale were not consistent with National Institutes of Health scores. Studies in the second samples showed the quenching of the acute phase reactions and the effectiveness of oxygen therapy. Only two of the examined APPs i.e. procalcitonin and transferrin, differed between surviving and non-surviving patients, and these two predispose to the role of prognostic factors in Covid-19. In conclusion, the concentration of not all acute-phase proteins depends on the severity of COVID-19 disease, presence of cytokine storm, the used of oxygen therapy and only some of them (procalcitonin and transferrin) are related to the survival outcomes. Of the newly tested acute-phase proteins, only transferrin shows significance as a marker of disease severity and mortality in COVID-19 disease.

Article URL: https://www.nature.com/articles/s41598-024-71325-2

Title

Resistance to SARS-CoV-2 infection in camelid nasal organoids is associated with lack of ACE2 expression

🤖 Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect different animals. How well an animal gets infected by SARS-CoV-2 depends on a special protein called ACE2 that the virus uses to enter cells. While SARS-CoV-2 can use many versions of the ACE2 protein found in various camel species, it doesn't make these camels sick when they are exposed to the virus. In this study, researchers used tiny living copies of parts of animals' noses (called organoids) to see if camels could be infected by SARS-CoV-2 or another related virus called MERS-CoV. The scientists found that while human nose copies can get infected with both viruses, camel nose copies don't. They also noticed something else: The camel nose copies had a different protein called DPP4 instead of ACE2. This led to the conclusion that because camels don't have enough of the ACE2 protein in their noses and upper respiratory tracts, they are resistant to SARS-CoV-2. So basically, it's like the virus can use other proteins found in camels' noses, but these aren't as good at letting the virus inside cells. Because of this, camels don't get sick from the virus even if they're exposed to it.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects a variety of animal species. Susceptibility to SARS-CoV-2 is primarily determined by the utilization of the viral receptor, ACE2. SARS-CoV-2 can utilize a broad range of animal ACE2 isoforms in vitro, including the ACE2 from various camelid species. However, experimental infection of these animals does not lead to productive infection or seroconversion. In this study, we investigate the susceptibility of camelids to SARS-CoV-2 using novel well-differentiated camelid nasal organoids. We show that camelid nasal organoids are highly susceptible to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, but not to infection with different SARS-CoV-2 variants (614G, BA.1 or EG.5.1.1). All viruses efficiently infected human airway organoids. Immunohistochemistry analysis revealed the absence of ACE2 on camelid nasal organoids and dromedary camel upper respiratory tract. In contrast, DPP4 was expressed in both camelid nasal organoids and the camel upper respiratory tract, which correlates with MERS-CoV infection. This study indicates that the camelid upper respiratory tract lacks expression of ACE2, which is associated with resistance to SARS-CoV-2 infection.

Article URL: https://www.nature.com/articles/s44298-024-00054-0

Title

T-cell responses to ancestral SARS-CoV-2 and Omicron variant among unvaccinated pregnant and postpartum women living with and without HIV in South Africa

🤖 Abstract

Here's a simplified version of the abstract: Scientists studied how people who are pregnant or have recently given birth and living with HIV react to COVID-19 in their bodies. They looked at 24 women without HIV and 15 women with HIV from low-income countries. The researchers found that these women's immune systems can fight off COVID-19 just as well as women who don't have HIV, even if they've never been vaccinated against the virus. They also discovered that the immune system's response to a specific part of the virus called Omicron is similar to its response to earlier versions of the virus. This means that people with COVID-19 can still get protection from their immune system, even if they haven't received a vaccine.

Abstract

SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated SARS-CoV-2-specific T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4+and CD8+T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV-2-specific T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4+and CD8+T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity.

Article URL: https://www.nature.com/articles/s41598-024-70725-8

Title

Investigation of risk factors for invasive pulmonary aspergillosis among patients with COVID-19

🤖 Abstract

Here's a simplified version of the abstract: Scientists studied 114 people who had COVID-19 and found that some developed a secondary infection called pulmonary aspergillosis (CAPA). This study looked for factors that might increase the risk of developing CAPA. The results showed that certain conditions, such as being on kidney transplant medication, having high levels of inflammation in the body, or needing to be on a ventilator for a long time, made it more likely for someone with COVID-19 to develop CAPA. The researchers found that three main factors were strongly linked to an increased risk of CAPA: high levels of inflammation in the body, low levels of immune cells called T-cells, and needing to be on a ventilator for a long time. Identifying these risk factors can help doctors start treatment earlier, which may improve outcomes for people with CAPA.

Abstract

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA.

Article URL: https://www.nature.com/articles/s41598-024-71455-7

Title

Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants

🤖 Abstract

Here's a simplified version of the abstract: Scientists have found that as COVID-19 spreads, it mutates and changes into different versions. This means that the antibodies created by our immune system when we get infected or vaccinated may not be able to recognize the virus if it changes too much. Researchers wanted to understand why this happens. They discovered a group of antibodies that can fight COVID-19, and found out how they work together with other parts of the immune system to target the virus. They also found out that these antibodies are already present in people who have never had COVID-19, but are more abundant in people who have recovered from the disease. However, when scientists tested these antibodies against a new variant of the virus called Omicron, they found out that it can evade their attack by making small changes to its structure. This suggests that the pressure from our immune system may be driving the evolution of the virus into more aggressive forms. These findings provide further evidence that the spread of COVID-19 and its variants is influenced by our immune response, and highlight the importance of continued research into understanding how our bodies fight the virus.

Abstract

Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.

Article URL: https://www.nature.com/articles/s41467-024-51770-3

Title

Post COVID-19 conditions in an Australian pediatric cohort, 3 months following a Delta outbreak

🤖 Abstract

Here's a simplified version of the abstract: Many kids got sick with COVID-19 during an outbreak in Australia, but not much was known about how it affected them later on. We asked parents to fill out an online survey 12 weeks after their child had recovered from COVID-19 and found that only a small number (about 1 in 10) were still experiencing symptoms or problems with daily activities. Out of those who reported ongoing issues, some kids had recovered by the time they saw a doctor, while others had existing conditions that got worse. A smaller group had something called Post-COVID Condition, which is similar to Long COVID. Our study found that most kids who got COVID-19 recovered quickly, but for those who didn't, it can be a significant burden. We also discovered some risk factors that make kids more likely to experience ongoing problems after COVID-19, such as being older than 11 and having pre-existing medical conditions.

Abstract

BackgroundPediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents.MethodsThe parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment.Findings1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID.InterpretationDuring an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention.ImpactOur study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity.

Article URL: https://www.nature.com/articles/s41390-024-03492-x

Title

Risk factors for mortality in hospitalized COVID-19 patients across five waves in Pakistan

🤖 Abstract

Here's a simplified version of the abstract: Researchers studied 5368 people who were hospitalized with COVID-19 in Pakistan over two years. They looked at how the virus affected different age groups and the outcomes for patients. They found that: * Older adults (aged 60+) made up a larger proportion of patients during certain waves of the pandemic. * Men were more likely to be infected earlier in the pandemic, but this changed later on. * The mortality rate (death rate) varied across different waves, with some being higher than others. * Certain conditions, such as acute respiratory distress syndrome and acute kidney injury, increased the risk of death. * Some patients who received a type of blood thinner called enoxaparin had lower odds of dying from COVID-19. The study suggests that older adults and those with certain health complications are at higher risk of dying from COVID-19 during certain waves of the pandemic.

Abstract

This retrospective cohort study aims to describe the clinical characteristics and outcomes and assess risk factors for mortality across the epidemic waves in hospitalized COVID-19 patients in a major tertiary-care center in Pakistan. A total of 5368 patients with COVID-19, hospitalized between March 2020 and April 2022 were included. The median age was 58 years (IQR: 44–69), 41% were females, and the overall mortality was 12%. Comparative analysis of COVID-19 waves showed that the proportion of patients aged ≥ 60 years was highest during the post-wave 4 period (61.4%) and Wave 4 (Delta) (50%) (p< 0.001). Male predominance decreased from 65.2% in Wave 2 to 44.2% in Wave 5 (Omicron) (p< 0.001). Mortality rate was lowest at 9.4% in wave 5 and highest at 21.6% in the post-wave 4 period (p= 0.041). In multivariable analysis for risk factors of mortality, acute respiratory distress syndrome (ARDS) was most strongly associated with mortality (aOR 22.98, 95% CI 15.28–34.55,p< 0.001), followed by need for mechanical ventilation (aOR 6.81, 95% CI 5.13–9.05,p< 0.001). Other significant risk factors included acute kidney injury (aOR 3.05, 95% CI 2.38–3.91,p< 0.001), stroke (aOR 2.40, 95% CI 1.26–4.60, p = 0.008), pulmonary embolism (OR 2.07, 95% CI 1.28–3.35,p= 0.003), and age ≥ 60 years (aOR 2.45, 95% CI 1.95–3.09,p< 0.001). Enoxaparin use was associated with lower mortality odds (aOR 0.45, 95% CI 0.35–0.60,p< 0.001. Patients hospitalized during Wave 4 (aOR 2.22, 95% CI 1.39–3.56,p< 0.001) and the post-wave 4 period (aOR 2.82, 95% CI 1.37–5.80,p= 0.005) had higher mortality odds compared to other waves. The study identifies higher mortality risk in patients admitted in Delta wave and post-wave, aged ≥ 60 years, and with respiratory and renal complications, and lower risk with anticoagulation during COVID-19 waves.

Article URL: https://www.nature.com/articles/s41598-024-70662-6

Title

A program for real-time surveillance of SARS-CoV-2 genetics

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 pandemic required scientists to quickly identify new variants of the virus. This meant setting up a nationwide system to collect, analyze, and report data on patient samples in a very short time frame. We developed an infrastructure that allowed us to sequence over 594,000 SARS-CoV-2 genomes from patients in the US between March 2020 and July 2023. Our protocol (called "Virseq") ensures accurate and reliable sequencing of the entire virus genome, even for multiple strains co-infecting a patient. This system supports the national surveillance program led by the CDC and serves as a model for responding to future pandemics quickly and effectively at a national scale.

Abstract

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.S.) from March 13th 2020 to July 3rd 2023. Our sequencing protocol (‘Virseq’) utilizes wet and dry lab procedures to generate mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control and Prevention national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale.

Article URL: https://www.nature.com/articles/s41598-024-70697-9

Title

Mapping the immunopeptidome of seven SARS-CoV-2 antigens across common HLA haplotypes

🤖 Abstract

Here's a simplified version of the abstract: Most COVID-19 vaccines currently work by teaching our bodies to fight the virus's "Spike" protein. However, new variants of the virus can make this Spike protein change shape and become harder for our immune systems to recognize. To address this issue, researchers are working on developing vaccines that target a broader range of proteins in the SARS-CoV-2 virus. To do this, scientists used a powerful tool called mass spectrometry to identify tiny pieces of these proteins (called "immunopeptides") that can trigger an immune response. They tested these immunopeptides against different versions of human cells and found 248 unique peptides that were bound to specific parts of the cell's surface. These findings could help create more effective COVID-19 vaccines by targeting multiple proteins in the SARS-CoV-2 virus, rather than just one protein like the Spike protein.

Abstract

Most COVID-19 vaccines elicit immunity against the SARS-CoV-2 Spike protein. However, Spike protein mutations in emerging strains and immune evasion by the SARS-CoV-2 virus demonstrates the need to develop more broadly targeting vaccines. To facilitate this, we use mass spectrometry to identify immunopeptides derived from seven relatively conserved structural and non-structural SARS-CoV-2 proteins (N, E, Nsp1/4/5/8/9). We use two different B-lymphoblastoid cell lines to map Human Leukocyte Antigen (HLA) class I and class II immunopeptidomes covering some of the prevalent HLA types across the global human population. We employ DNA plasmid transfection and direct antigen delivery approaches to sample different antigens and find 248 unique HLA class I and HLA class II bound peptides with 71 derived from N, 12 from E, 28 from Nsp1, 19 from Nsp4, 73 from Nsp8 and 45 peptides derived from Nsp9. Over half of the viral peptides are unpublished. T cell reactivity tested against 56 of the detected peptides shows CD8+and CD4+T cell responses against several peptides from the N, E, and Nsp9 proteins. Results from this study will aid the development of next-generation COVID vaccines targeting epitopes from across a number of SARS-CoV-2 proteins.

Article URL: https://www.nature.com/articles/s41467-024-51959-6

Title

Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: Scientists conducted an experiment to test the effectiveness of a vaccine (mRNA-1273) in preventing COVID-19. The results showed that the vaccine was safe and worked well at preventing the disease in adults over 18 years old. To see if another dose of the vaccine (called a booster) would help even more, researchers gave some people an extra dose after they had already received their first shots. They found that this booster shot helped prevent COVID-19, especially during times when new and more contagious variants of the virus were spreading. The study also showed that the longer people waited between getting their first vaccine doses and receiving the booster, the better protected they were from getting COVID-19 again. Furthermore, the researchers found that people who received the booster had a stronger immune response against the virus than those who only got the initial shots. Overall, this study suggests that vaccination with mRNA-1273, including a booster dose, is a safe and effective way to protect against COVID-19, even when new variants are present.

Abstract

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites. The open-label (Parts B and C) primary objectives were evaluation of long-term safety and effectiveness of primary vaccination plus a 50-µg booster dose; immunogenicity was a secondary objective. Of 29,035 open-label participants, 19,609 received boosters (mRNA-1273 [n= 9647]; placebo-mRNA-1273 [n= 9952]; placebo [n= 10] groups). Booster safety was consistent with that reported for primary vaccination. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with a significant, 47.0% (95% CI : 39.0-53.9%) reduction of Omicron BA.1 incidence (24.6 [23.4 − 25.8] vs 46.4 [40.6 − 52.7]/1000 person-months). In an exploratory Cox regression model adjusted for time-varying covariates, a longer median interval between primary vaccination and boosting (mRNA-1273 [13 months] vs placebo-mRNA-1273 [8 months]) was associated with significantly lower, COVID-19 risk (24.0% [16.0% − 32.0%]) during Omicron BA.1 predominance. Boosting elicited greater immune responses against SARS-CoV-2 than primary vaccination, irrespective of prior SARS-CoV-2 infection. Primary vaccination and boosting with mRNA-1273 demonstrated acceptable safety, effectiveness and immunogenicity against COVID-19, including emergent variants.

Article URL: https://www.nature.com/articles/s41467-024-50376-z

Title

Early biological markers of post-acute sequelae of SARS-CoV-2 infection

🤖 Abstract

Here's a simplified version of the abstract: Scientists studied 136 people who had just tested positive for COVID-19 to understand why some people get long-term symptoms after the initial illness. They collected nasal swabs and blood samples over several weeks and found that people who developed long-term symptoms (called PASC) had higher levels of the virus in their bodies and lower antibodies against it, especially within the first 9 days of getting sick. This suggests that how the body responds to COVID-19 early on may play a role in whether someone develops long-term symptoms.

Abstract

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Article URL: https://www.nature.com/articles/s41467-024-51893-7

Title

An unexpected IgE anti-receptor binding domain response following natural infection and different types of SARS-CoV-2 vaccines

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: When people get infected with COVID-19 or vaccinated against it, their bodies produce special proteins called antibodies to fight the virus. Most research has focused on one type of antibody, but there are other types too. This study looked at a different type of antibody called IgE, which is usually associated with allergies and parasites. The researchers took blood samples from 59 people in Brazil who had been infected with COVID-19 or vaccinated against it. They found that IgE antibodies were produced after infection and vaccination. The good news was that the vaccines helped increase the levels of these antibodies, making them more effective at fighting the virus. The study also found that different types of vaccines worked better than others in producing IgE antibodies. However, when people got a booster shot with a third vaccine, their IgE antibody levels became similar across all groups. Overall, this study suggests that IgE antibodies play an important role in our immune system's response to COVID-19 and viruses, and more research is needed to understand how they work and their potential benefits.

Abstract

Humoral response to SARS-CoV-2 has been studied, predominantly the classical IgG and its subclasses. Although IgE antibodies are typically specific to allergens or parasites, a few reports describe their production in response to SARS-CoV-2 and other viruses. Here, we investigated IgE specific to receptor binding domain (RBD) of SARS-CoV-2 in a Brazilian cohort following natural infection and vaccination. Samples from 59 volunteers were assessed after infection (COVID-19), primary immunization with vectored (ChAdOx1) or inactivated (CoronaVac) vaccines, and booster immunization with mRNA (BNT162b2) vaccine. Natural COVID-19 induced IgE, but vaccination increased its levels. Subjects vaccinated with two doses of ChAdOx1 exhibited a more robust response than those immunized with two doses of CoronaVac; however, after boosting with BNT162b2, all groups presented similar IgE levels. IgE showed intermediate-to-high avidity, especially after the booster vaccine. We also found IgG4 antibodies, mainly after the booster, and they moderately correlated with IgE. ELISA results were confirmed by control assays, using IgG depletion by protein G and lack of reactivity with heterologous antigen. In our cohort, no clinical data could be associated with the IgE response. We advocate for further research on IgE and its role in viral immunity, extending beyond allergies and parasitic infections.

Article URL: https://www.nature.com/articles/s41598-024-71047-5

Title

Fibrin drives thromboinflammation and neuropathology in COVID-19

🤖 Abstract

Here's a simplified version of the abstract: Some people who get COVID-19 develop blood clots that can be life-threatening, as well as brain symptoms like memory loss or confusion. This can happen even after they've recovered from the virus. Despite this, scientists still don't fully understand why it happens and there aren't enough treatments. A protein called fibrin, which helps form blood clots, is found in high amounts in the lungs and brains of people with COVID-19. It's also a good indicator of how severe their symptoms will be and can predict brain problems after they've recovered. Scientists have discovered that fibrin binds to the COVID-19 virus and forms pro-inflammatory blood clots, which causes more inflammation and damage to the brain and lungs. They've also found that targeting this part of the fibrin protein with a special antibody can help protect against further damage. This suggests that targeting fibrin could be a new way to treat not only acute COVID-19 but also long-term symptoms after recovery.

Abstract

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1,2,3,4. Despite the clinical evidence1,5,6,7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8,9,10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

Article URL: https://www.nature.com/articles/s41586-024-07873-4

Title

Antibody Fc receptor binding and T cell responses to homologous and heterologous immunization with inactivated or mRNA vaccines against SARS-CoV-2

🤖 Abstract

Here's a simplified version of the abstract: Two different COVID-19 vaccines, CoronaVac and BNT162b2 (also known as Pfizer-BioNTech), were tested in a study to see how well they worked against severe illness from COVID-19. The results showed that while both vaccines are effective in preventing serious illness, they work differently inside the body. The researchers looked at how well each vaccine stimulated the immune system to produce antibodies and T cells, which help fight off the virus. They found that: * BNT162b2 (Pfizer-BioNTech) booster shots produced more antibodies against COVID-19 than CoronaVac booster shots. * Participants who received CoronaVac as a first dose had lower levels of certain immune cells called CD4+IFNγ+cells, but this level increased after receiving either CoronaVac or BNT162b2 booster shots. * The type of vaccine used for the first dose (CoronaVac or Pfizer-BioNTech) influenced which types of T cells and antibodies were produced by the body. These findings suggest that while both vaccines have their strengths and weaknesses, they can still provide protection against severe COVID-19 illness.

Abstract

Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+IFNγ+cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.

Article URL: https://www.nature.com/articles/s41467-024-51427-1

Title

Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens

🤖 Abstract

Here's a simplified version of the abstract: The COVID-19 vaccine works by using a special part of the virus called the spike (S) to help our bodies fight it. However, the virus can change over time and become harder for the vaccine to recognize. The stable part of the spike is called S2, which doesn't change much and can trigger strong antibodies in our bodies that can protect us against different types of viruses. But, this part of the spike is difficult to keep stable and has been hard to use as a vaccine. We used computer simulations to design a new version of S2 that is more stable and still triggers strong antibodies. Our results show that this new version works well in tests and could be an effective alternative to traditional COVID-19 vaccines.

Abstract

The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2’s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer’s opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

Article URL: https://www.nature.com/articles/s41467-024-50976-9

Title

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial

🤖 Abstract

Here's a simplified version of the abstract: Scientists wanted to see if inhaling a medicine called inhaled enriched heparin can help treat COVID-19. They tested it on 27 hospitalized adults with COVID-19 and compared them to people who got a placebo (a fake treatment). The results showed that inhaling this medicine was safe and helped reduce the need for oxygen and improved lung function in patients. These promising findings mean they want to continue testing it in even larger groups of people to see if it's truly effective in treating COVID-19.

Abstract

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Article URL: https://www.nature.com/articles/s41598-024-70064-8

Title

Neutralizing and binding antibody responses to SARS-CoV-2 with hybrid immunity in pregnancy

🤖 Abstract

Here's a simplified version of the abstract: When pregnant women get vaccinated against COVID-19 or catch the virus, their bodies make antibodies that can help protect them and their babies. Researchers studied how well these antibodies worked after different combinations of vaccination and infection during pregnancy. They found that when women got three doses of the vaccine, it boosted the level of protective antibodies more than just two doses or getting infected with COVID-19 alone. This effect was even stronger when women had both vaccinated and been infected. The researchers also looked at how well these antibodies were transferred from mother to baby during pregnancy. They found that antibodies made by the vaccine were passed on more efficiently than those made by infection. These findings suggest that combining vaccination and natural immunity can create a stronger defense against COVID-19 in pregnant women, which is good news for protecting both mom and baby!

Abstract

Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy.

Article URL: https://www.nature.com/articles/s41541-024-00948-3

Title

A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants

🤖 Abstract

Here's a simplified version of the abstract that a young person can understand: COVID-19, caused by the SARS-CoV-2 virus, continues to affect people worldwide and cause significant health and economic problems. Despite vaccines being effective in preventing severe cases, there is still no guarantee against new variants of the virus or unexpected breakthrough infections. Researchers have developed a new vaccine called CDO-7N-1 that uses a weakened form of the SARS-CoV-2 virus to stimulate an immune response. In laboratory tests, this vaccine has been shown to provide long-lasting protection against different strains of the virus and prevent lung damage. A single dose of the vaccine triggered a strong immune response in mice, hamsters, and macaques, protecting them from infection with wild-type SARS-CoV-2 and other variants of concern. The researchers believe that this new vaccine could improve immunity against future SARS-CoV-2 variants and provide better protection for people worldwide.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.

Article URL: https://www.nature.com/articles/s41467-024-51535-y

Title

SARS-CoV-2 infection results in a unique lung proteome long after virus resolution in the hamster

🤖 Abstract

Here's a simplified version of the abstract: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a condition where people experience ongoing problems after having COVID-19. It can make it hard for them to contribute to society. To understand why this happens, researchers studied the lung proteins in hamsters infected with an early version of the SARS-CoV-2 virus. They found that at 3 and 5 days after infection, many lung proteins changed in both male and female hamsters. However, by day 31 (when no virus was left), they saw differences between the sexes, including some proteins that were lower or higher in males than females. The researchers also found that biological sex should be considered when developing treatments for PASC because of these differences.

Abstract

Long COVID or post-acute sequelae of COVID-19 (PASC) remains an ongoing public health issue that causes impairment for those afflicted and diminishes their ability to contribute to society. To address the host response underpinning respiratory PASC, we used the Golden Syrian hamster model infected with ancestral SARS-CoV-2 and examined its lung proteome in a longitudinal experiment. We infected young 6-week old male and female hamsters with 105TCID50of virus via the intranasal route and sampled the lung at 1, 3, 5, and 31 days post infection (dpi). We compared the infected lung proteome to that of uninfected sex-matched controls. We found almost no differences in protein levels at 1 dpi, with hundreds at 3 dpi, and thousands at 5 dpi. Many overlapping differential protein levels and pathways were seen in both sexes at 3 and 5 dpi including the Coagulation and Complement cascades. Notably, we found differences between the sexes at 31 dpi which included many targets with decreased levels of protein in the males. We also noted an increase in 7 proteins in both sexes at 31 dpi including proteins responsible for airway mucosal layer integrity such as Mucin 5B and Calcium-activated chloride channel regulator 1. Longitudinally, 38 proteins were changed in levels across more than one timepoint in the males but only three proteins were in the females, Secretoglobin family 1 A member 1, Poly [ADP-ribose] polymerase, and Apolipoprotein D. Overall, we show that there are changes to the lung proteome at 31 dpi, a time when no SARS-CoV-2 remains, and that there are sex differences in that proteome after infection with the ancestral strain. We conclude that biological sex should be examined as a variable when testing medical countermeasures for PASC in the Golden Syrian hamster due to host differences between the sexes.

Article URL: https://www.nature.com/articles/s44298-024-00049-x

Title

Premature aging effects on COVID-19 pathogenesis: new insights from mouse models

🤖 Abstract

Here's a simplified version of the abstract: As we get older, our bodies become more vulnerable to severe illnesses like COVID-19. The connection between age, existing health problems, and COVID-19 is not fully understood. This study used a special mouse model that ages quickly to see how COVID-19 affects different age groups. The results showed that younger mice can fight off the virus easily, but older mice have a weaker response and are more likely to get very sick and die. The mouse model with premature aging showed milder symptoms, but still had some problems with their immune system and metabolism. By studying how COVID-19 affects these mice, scientists hope to gain a better understanding of why some people are more susceptible to severe illness and develop new treatments for COVID-19 and other diseases related to aging.

Abstract

Aging is identified as a significant risk factor for severe coronavirus disease-2019 (COVID-19), often resulting in profound lung damage and mortality. Yet, the biological relationship between aging, aging-related comorbidities, and COVID-19 remains incompletely understood. This study aimed to elucidate the age-related COVID19 pathogenesis using an Hutchinson-Gilford progeria syndrome (HGPS) mouse model, a premature aging disease model, with humanized ACE2 receptors. Pathological features were compared between young, aged, and HGPS hACE2 mice following SARS-CoV-2 challenge. We demonstrated that young mice display robust interferon response and antiviral activity, whereas this response is attenuated in aged mice. Viral infection in aged mice results in severe respiratory tract hemorrhage, likely contributing a higher mortality rate. In contrast, HGPS hACE2 mice exhibit milder disease manifestations characterized by minor immune cell infiltration and dysregulation of multiple metabolic processes. Comprehensive transcriptome analysis revealed both shared and unique gene expression dynamics among different mouse groups. Collectively, our studies evaluated the impact of SARS-CoV-2 infection on progeroid syndromes using a HGPS hACE2 mouse model, which holds promise as a useful tool for investigating COVID-19 pathogenesis in individuals with premature aging.

Article URL: https://www.nature.com/articles/s41598-024-70612-2

Title

Non-human primate model of long-COVID identifies immune associates of hyperglycemia

🤖 Abstract

Hyperglycemia happens when your body has trouble using sugar after catching a severe illness like COVID-19. Scientists don't understand this very well in people, so they used monkeys infected with the same virus to study it better. They found that shortly after getting sick, the blood of these monkeys had changes called "chemokines" that could lead to high sugar levels. Four months later, this still happened in most of them. High sugar is linked to something called glycogen in the liver and pancreas. But they didn't see the virus living in those parts anymore. They also tested a vaccine for COVID-19 given to monkeys on day 4 after infection. The monkey's blood sugar levels went down as a result. These findings suggest that studying these infected monkeys can help understand what happens when people get sick from this illness, and how we might treat it better.

Abstract

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

Article URL: https://www.nature.com/articles/s41467-024-50339-4

Title

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia

🤖 Abstract

This study looked at how certain pieces of machinery that help make RNA (a type of molecule important for cells) work less effectively when someone has COVID-19. When the researchers found there were fewer of these pieces, they had more trouble with their lungs getting sick from the virus. The study showed that a protein made by the virus also makes these pieces disappear faster. This leads to problems like DNA damage and lung issues. They also noticed older people have less of these pieces in their lungs, making them sicker when infected. Two types of medicine helped make the sickness better. The main points are: - Certain RNA-making parts don't work well in COVID patients. - The virus causes fewer of these parts to be made. - This makes it harder for cells to repair themselves and function properly. - Older people get more sick because they have less of these parts. - Special medicines can help.

Abstract

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Article URL: https://www.nature.com/articles/s41467-024-51192-1

Title

Atypical and non-classical CD45RBlomemory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19

🤖 Abstract

The resting memory B cells are divided into two main groups: classical and atypical. Classical cells stay the same after being activated. Atypical cells can be further split into two types: one with CD11c on their surface, and another with CD23. When someone gets a vaccine or gets sick from bacteria, these resting memory B cells help make antibodies that fight the virus. In both scenarios, atypical cells called CD45RBlo play a big role in making antibodies against SARS-CoV-2. Our findings suggest that tracking the levels of CD45RB on these cells can help us understand how they work and contribute to getting vaccinated or recovering from infections like COVID-19.

Abstract

Resting memory B cells can be divided into classical or atypical groups, but the heterogenous marker expression on activated memory B cells makes similar classification difficult. Here, by longitudinal analysis of mass cytometry and CITE-seq data from cohorts with COVID-19, bacterial sepsis, or BNT162b2 mRNA vaccine, we observe that resting B cell memory consist of classical CD45RB+memory and CD45RBlomemory, of which the latter contains of two distinct groups of CD11c+atypical and CD23+non-classical memory cells. CD45RB levels remain stable in these cells after activation, thereby enabling the tracking of activated B cells and plasmablasts derived from either CD45RB+or CD45RBlomemory B cells. Moreover, in both COVID-19 patients and mRNA vaccination, CD45RBloB cells formed the majority of SARS-CoV2 specific memory B cells and correlated with serum antibodies, while CD45RB+memory are activated by bacterial sepsis. Our results thus identify that stably expressed CD45RB levels can be exploited to trace resting memory B cells and their activated progeny, and suggest that atypical and non-classical CD45RBlomemory B cells contribute to SARS-CoV-2 infection and vaccination.

Article URL: https://www.nature.com/articles/s41467-024-50997-4

Title

Multi-omics characterization of the monkeypox virus infection

🤖 Abstract

We studied how monkeypox (MPXV) virus affects human cells using different types of genetic analysis. We found that the virus changes many pathways in the infected cells, including those related to immune responses and cell growth. One interesting thing we noticed is that MPXV causes changes in proteins involved in cell signaling. Specifically, we saw how it can affect a protein called H5 which interacts with DNA. We also used this data to look for new treatments that could stop the virus from growing inside cells. By looking at all these different pathways and interactions, we found some promising targets like MTOR, CHUK/IKBKB, and splicing factor kinases, which seem to have strong effects against both monkeypox and another similar virus called vaccinia (VACV). Overall, our study helps us understand how these viruses affect cells and opens up new possibilities for finding treatments.

Abstract

Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-β pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.

Article URL: https://www.nature.com/articles/s41467-024-51074-6

Title

Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death

🤖 Abstract

Effective ways to prevent problems after getting sick from COVID are important for people, doctors, and governments. This study looked at how things like exercise, diet, sleep, smoking, drinking, being a healthy weight, and eating well can affect someone's health years later. People who had more healthy habits were less likely to get many different kinds of long-term sicknesses related to COVID. They also had a lower risk of dying or needing hospitalization after getting sick from COVID. These healthier habits worked even for people who didn't get very sick in the first place. The study found that following these healthy habits was really important and not just because they might have had fewer other health problems before catching COVID. This means it's good to keep up with a healthy lifestyle, no matter what, to help prevent long-term sickness from COVID. These findings show how keeping fit and eating well can be very helpful in the future for dealing with possible new pandemics.

Abstract

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n= 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness.

Article URL: https://www.nature.com/articles/s41467-024-50495-7

Title

Efficacy of the tetravalent protein COVID-19 vaccine, SCTV01E: a phase 3 double-blind, randomized, placebo-controlled trial

🤖 Abstract

This study tested a new type of vaccine called SCTV01E that can protect against four different strains of coronavirus (SARS-CoV-2). The goal was to see if it works by comparing how many people got sick with the virus when given the vaccine versus not getting the vaccine. They gave the vaccine to 9,223 people and had them wait for seven days. They found that the vaccine worked very well in preventing someone from getting sick: about two-thirds of people who didn't get vaccinated got sick compared to only one-third who did get the vaccine. It also helped protect against all kinds of coronavirus infections. The vaccine was safe, with most side effects being mild and short-lived. The researchers think this type of vaccine might work well against new strains that appear over time.

Abstract

Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Article URL: https://www.nature.com/articles/s41467-024-49832-7

Title

Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein

🤖 Abstract

SARS-CoV-2 makes people sick partly by causing an overreaction in their lungs that leads to more inflammation. This inflammation can last for a long time after the virus is gone, which some doctors call "Long COVID." The virus also stops another system called CFTR from working properly in lung cells. CFTR helps keep the lungs moist and healthy. When this doesn't work, it causes problems similar to a condition called cystic fibrosis. We think SARS-CoV-2 might be stopping CFTR because of something on its surface called spike protein. This could happen by blocking another system on the cell surface that normally helps fix CFTR. Our experiments showed that when lung cells are exposed to this virus, they lose their ability to make and use a healthy version of CFTR. Without CFTR working properly, cells start making too much of two other things that cause inflammation: NFκB and ENaC. We found that adding certain drugs called cardiac glycosides can help keep the cells' CFTR from disappearing when exposed to the virus. These drugs might be important for treating "Long COVID" as well. Overall, our experiments suggest that SARS-CoV-2's spike protein stops a healthy system in lung cells (CFTR) from working properly, which could lead to inflammation and possibly cause symptoms of "Long COVID.

Abstract

SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper-proinflammatory state involves activation of signaling by NFκB, and unexpectedly, ENaC, the epithelial sodium channel. Post-infection inflammation may also contribute to "Long COVID"/PASC. Enhanced signaling by NFκB and ENaC also marks the airway of patients suffering from cystic fibrosis, a life-limiting proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 spike protein, and therefore activation of both NFκB and ENaC signaling. We used western blot and electrophysiological techniques, and an organoid model of normal airway epithelia, differentiated on an air–liquid-interface (ALI). We found that CFTR protein expression and CFTR cAMP-activated chloride channel activity were lost when the model epithelium was exposed to SARS-CoV-2 spike proteins. As hypothesized, the absence of CFTR led to activation of both TNFα/NFκB signaling and α and γ ENaC. We had previously shown that the cardiac glycoside drugs digoxin, digitoxin and ouabain blocked interaction of spike protein and ACE2. Consistently, addition of 30 nM concentrations of the cardiac glycoside drugs, prevented loss of both CFTR protein and CFTR channel activity. ACE2 and CFTR were found to co-immunoprecipitate in both basal cells and differentiated epithelia. Thus spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane. Thus, failure of CFTR recovery from endosomal recycling might be a mechanism for spike-dependent loss of CFTR. Finally, we found that authentic SARS-CoV-2 virus infection induced loss of CFTR protein, which was rescued by the cardiac glycoside drugs digitoxin and ouabain. Based on experiments with this organoid model of small airway epithelia, and comparisons with 16HBE14o- and other cell types expressing normal CFTR, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by the SARS-CoV-2 spike protein, thus inducing a cystic fibrosis-like clinical phenotype. To our knowledge this is the first time COVID-19 airway inflammation has been experimentally traced in normal subjects to a contribution from SARS-CoV-2 spike-dependent inhibition of CFTR signaling.

Article URL: https://www.nature.com/articles/s41598-024-66473-4

Title

Insights from an N3C RECOVER EHR-based cohort study characterizing SARS-CoV-2 reinfections and Long COVID

🤖 Abstract

### ABSTRACT SIMPLIFIED The pandemic is still going on for over 3 years, but doctors don't fully know about getting sick with a virus called SARS-CoV-2 more than once. We studied lots of people's health records to learn more. We found that: - Most reinfections happened during the Omicron wave. - People who got infected twice had more Long COVID (a long-term sickness) compared to those who only got it once in the same period. - Before you get reinfected, your body might not have as much protein. - Getting a bad first infection also makes the second one worse. - Older people and those at higher risk of dying are more likely to have a severe second infection if they had a bad first one. This helps us understand reinfections better so we can find new ways to help people who get sick again.

Abstract

BackgroundAlthough the COVID-19 pandemic has persisted for over 3 years, reinfections with SARS-CoV-2 are not well understood. We aim to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection.MethodsWe use an electronic health record study cohort of over 3 million patients from the National COVID Cohort Collaborative as part of the NIH Researching COVID to Enhance Recovery Initiative. We calculate summary statistics, effect sizes, and Kaplan–Meier curves to better understand COVID-19 reinfections.ResultsHere we validate previous findings of reinfection incidence (6.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present findings that the proportion of Long COVID diagnoses is higher following initial infection than reinfection for infections in the same epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between initial infection and reinfection (chi-squared value: 25,697,p-value: <0.0001) with a medium effect size (Cramer’sV: 0.20, DoF = 3). Individuals who experienced severe initial and first reinfection were older in age and at a higher mortality risk than those who had mild initial infection and reinfection.ConclusionsIn a large patient cohort, we find that the severity of reinfection appears to be associated with the severity of initial infection and that Long COVID diagnoses appear to occur more often following initial infection than reinfection in the same epoch. Future research may build on these findings to better understand COVID-19 reinfections.

Article URL: https://www.nature.com/articles/s43856-024-00539-2

Title

Selection and characterization of human scFvs targeting the SARS-CoV-2 nucleocapsid protein isolated from antibody libraries of COVID-19 patients

🤖 Abstract

In 2019, a new coronavirus called SARS-CoV-2 appeared in China and caused an illness called COVID-19. At first, scientists mainly studied the spike protein. But they later found out that another part of the virus, called the nucleocapsid (N) protein, is very important for spreading the disease and fighting off our immune system. Scientists decided to create a collection of special antibodies against this N protein using patients who had been infected with SARS-CoV-2. They used a new technology to pick out some strong antibody parts called single chain fragments variable (scFvs). These scFvs can be made into different forms like tiny intrabodies inside cells or as regular proteins outside the cells. They found that some of these antibodies work very well when they are inside cells, and others work even better when they are made separately from the cell. All of them can stick to the N protein with a strong grip. This collection of powerful N protein antibodies is new and could help in research and making tests for detecting SARS-CoV-2. So basically, scientists got some really good tools to fight against this virus by studying its parts more closely.

Abstract

In 2019, the novel SARS-CoV-2 coronavirus emerged in China, causing the pneumonia named COVID-19. At the beginning, all research efforts were focused on the spike (S) glycoprotein. However, it became evident that the nucleocapsid (N) protein is pivotal in viral replication, genome packaging and evasion of the immune system, is highly immunogenic, which makes it another compelling target for antibody development alongside the spike protein. This study focused on the construction of single chain fragments variable (scFvs) libraries from SARS-CoV-2-infected patients to establish a valuable, immortalized and extensive antibodies source. We used the Intracellular Antibody Capture Technology to select a panel of scFvs against the SARS-CoV-2 N protein. The whole panel of scFv was expressed and characterized both as intrabodies and recombinant proteins. ScFvs were then divided into 2 subgroups: those that exhibited high binding activity to N protein when expressed in yeast or in mammalian cells as intrabodies, and those purified as recombinant proteins, displaying affinity for recombinant N protein in the nanomolar range. This panel of scFvs against the N protein represents a novel platform for research and potential diagnostic applications.

Article URL: https://www.nature.com/articles/s41598-024-66558-0

Title

A particular epidemiological profile: disparities in access to contraceptive methods in Brazil during the SARS-CoV-2 (COVID-19) pandemic

🤖 Abstract

The study looked at how easier or harder it was for people to get birth control during the pandemic in Brazil. They surveyed about 1000 young adults aged 20-39 who use contraception there. Most respondents were women, white, and using some form of birth control. Many people changed their birth control method during the pandemic. But more than a quarter said they had trouble finding information on new methods or seeing healthcare providers to get help with their current birth control. The survey found that younger black and biracial women with less education and income faced bigger challenges getting access to contraception and family planning services.

Abstract

Our objective was to study disparities in access to contraception during the COVID-19 pandemic. We performed a cross-sectional study at the University of Campinas, Brazil using a Google questionnaire applied from December 2021 until February 2022, disseminated via snowball technique. The survey asked about sociodemographic characteristics and contraceptive use, as well as the demand for new methods and difficulties in continuing to use contraceptives during the COVID-19 pandemic. We analyzed 1018 completed questionnaires; in total, 742 (72.9%) were women aged between 20 and 39 years, 746 (73.3%) were White and 602 (59.2%) used contraceptives. During the COVID-19 pandemic, about 23% of respondents changed their method and approximately 20% of respondents looked for new methods. Among the latter, 31.3% reported some difficulty with obtaining guidance on new methods while only 5.3% of the respondents reported some difficulty with continuing their contraceptive. The main difficulty in both cases was the difficulty with getting a healthcare provider appointment. Our results point to a particular epidemiological population, of younger black and biracial women, with lower education and lower income, which suffered health disparities during the COVID-19 pandemic and found difficulties with using contraceptives and accessing family planning services.

Article URL: https://www.nature.com/articles/s41598-024-65946-w

Title

SARS-CoV-2 antigenemia and RNAemia in association with disease severity in patients with COVID-19

🤖 Abstract

### ABSTRACT REWRITTEN Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes different sickness levels from mild to severe. We studied how this virus affects people and what parts of the body it gets into. In our study, we looked at two things: when certain parts of the virus show up in a person's blood (antigenemia), and when its genetic material is detectable (RNAemia). We examined 117 patients with confirmed COVID-19. Their ages ranged from around 52 to 79 years old, with more males than females. We found that in people who died early, the virus parts showed up very fast within a week after they were admitted. When we looked at how these virus parts show up over time: - They showed up in everyone's blood (100%) by the first week. - At admission, they could be seen 64.7% of the time but correctly identified as being there 73% of the time. - In the second week, they were spotted in about 69% of people and correctly detected in all cases. We also saw that sick patients who had no symptoms at first (asymptomatic) still showed antigenemia. But by the end of the first week, none of them did anymore. The virus genetic material was found more often in people who died than in those who were just mildly sick. Looking at how long people lived after being admitted: - People with higher levels of these parts showing up in their blood had a worse chance of surviving. - This finding suggests that if the virus parts show up quickly, it might mean someone is more likely to die early.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections.However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0–79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan–Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P= 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Article URL: https://www.nature.com/articles/s41598-024-65489-0

Title

SARS-CoV-2 viral titer measurements in Ontario, Canada wastewaters throughout the COVID-19 pandemic

🤖 Abstract

During the COVID-19 pandemic in Canada, Ontario started checking water from sewers to see if people had coronavirus. They did this starting from January 2021 until March 2023 by looking at samples from different places across the province. These samples came from more than half of Ontario’s population and some parts of Canada. The team checked things like where these places were, how many people they served, what kind of water it was, and how much water flowed through. They did this test 2 to 7 times a week at each place. This helps them understand if coronavirus is spreading in different areas. It's especially useful now that the Omicron variant is around and fewer people are getting sick enough to be tested in hospitals. The team saved all this information so they can use it for research and planning for future sicknesses. The data from these sewer samples has been very helpful for keeping track of coronavirus cases across Ontario.

Abstract

During the COVID-19 pandemic, the Province of Ontario, Canada, launched a wastewater surveillance program to monitor SARS-CoV-2, inspired by the early work and successful forecasts of COVID-19 waves in the city of Ottawa, Ontario. This manuscript presents a dataset from January 1, 2021, to March 31, 2023, with RT-qPCR results for SARS-CoV-2 genes and PMMoV from 107 sites across all 34 public health units in Ontario, covering 72% of the province’s and 26.2% of Canada’s population. Sampling occurred 2–7 times weekly, including geographical coordinates, serviced populations, physico-chemical water characteristics, and flowrates. In doing so, this manuscript ensures data availability and metadata preservation to support future research and epidemic preparedness through detailed analyses and modeling. The dataset has been crucial for public health in tracking disease locally, especially with the rise of the Omicron variant and the decline in clinical testing, highlighting wastewater-based surveillance’s role in estimating disease incidence in Ontario.

Article URL: https://www.nature.com/articles/s41597-024-03414-w

Title

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents

🤖 Abstract

The abstract talks about how certain immune cells (T cells) in people who had COVID-19 can recognize other coronaviruses like SARS as well. We tested these T cells to see which parts of the viruses they could react with, and found that they mostly reacted to parts of the virus that don't change much between different strains. This means existing antibodies against one type of coronavirus might help protect against others. Our findings could help develop vaccines for multiple types of coronaviruses in the future.

Abstract

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

Article URL: https://www.nature.com/articles/s41392-024-01876-3

Title

Tracking the evolution of anti-SARS-CoV-2 antibodies and long-term humoral immunity within 2 years after COVID-19 infection

🤖 Abstract

The virus that causes COVID-19 makes people very sick sometimes. The body's immune system produces special proteins called antibodies to fight the virus. Antibodies can either be made against parts of the virus that cover it, called spike proteins, or against another part inside the virus, called nucleocapsid. Scientists wanted to understand how long these antibodies last after someone recovers from COVID-19. They looked at people who had recovered and checked their blood over a year-long period. They found that antibodies against one part of the virus (nucleocapsid) stayed high for about 4 months, but then started going down a bit. Antibodies against another part of the virus (spike) kept increasing every few months until the end of the study. So, some parts of the body's defense against COVID-19 last longer than others. The scientists learned that certain antibodies stay strong for several months after someone recovers, while other antibodies keep growing stronger over time.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that gave rise to COVID-19 infection produced a worldwide health crisis. The virus can cause a serious or even fatal disease. Comprehending the complex immunological responses triggered by SARS-CoV-2 infection is essential for identifying pivotal elements that shape the course of the disease and its enduring effects on immunity. The span and potency of antibody responses provide valuable perspicuity into the resilience of post-infection immunity. The analysis of existing literature reveals a diverse controversy, confining varying data about the persistence of particular antibodies as well as the multifaceted factors that impact their development and titer, Within this study we aimed to understand the dynamics of anti-SARS-CoV-2 antibodies against nucleocapsid (anti-SARS-CoV-2 (N)) and spike (anti-SARS-CoV-2 (N)) proteins in long-term immunity in convalescent patients, as well as the factors influencing the production and kinetics of those antibodies. We collected 6115 serum samples from 1611 convalescent patients at different post-infection intervals up to 21 months Study showed that in the fourth month, the anti-SARS-CoV-2 (N) exhibited their peak mean value, demonstrating a 79% increase compared to the initial month. Over the subsequent eight months, the peak value experienced a modest decline, maintaining a relatively elevated level by the end of study. Conversely, anti-SARS-CoV-2 (S) exhibited a consistent increase at each three-month interval over the 15-month period, culminating in a statistically significant peak mean value at the study’s conclusion. Our findings demonstrate evidence of sustained seropositivity rates for both anti-SARS-CoV-2 (N) and (S), as well as distinct dynamics in the long-term antibody responses, with anti-SARS-CoV-2 (N) levels displaying remarkable persistence and anti-SARS-CoV-2 (S) antibodies exhibiting a progressive incline.

Article URL: https://www.nature.com/articles/s41598-024-64414-9

Title

Titers of IgG and IgA against SARS-CoV-2 proteins and their association with symptoms in mild COVID-19 infection

🤖 Abstract

The study looked at how antibodies in people with mild COVID-19 disease change over time. Antibodies are like the body's protection against viruses. They can be made into two types: IgG and IgA. The research found that different levels of these antibodies could predict if someone would get worse symptoms from COVID-19, like trouble breathing. They found that people with more severe symptoms had lower levels of certain antibodies. For example, people who couldn't breathe well had fewer antibodies against some parts of the virus compared to those who didn't have trouble breathing. Overall, the study suggests that how strong your antibody response is can tell you if you might get sicker from COVID-19 and what part of the virus causes problems for different symptoms.

Abstract

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM − samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

Article URL: https://www.nature.com/articles/s41598-024-59634-y

Title

Three-year outcomes of post-acute sequelae of COVID-19

🤖 Abstract

The virus that causes COVID-19 can cause long-term effects even after you get better from it. Researchers studied 135,000 people who had COVID and compared them to 5 million others over a 3-year period. They found that while the risk of dying went down for people who didn't need hospital care, those who did still had higher chances of death in the third year after getting sick. For hospitalized patients, their long-term risks were even more severe: they still had twice the chance of death compared to healthy people, and there was a lot of health loss that continued into the third year. Overall, most risks went down over time, but those who were hospitalized had high risks in the third year which led to significant health problems.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 years but still contributed 9.6 (95% confidence interval (CI): 0.4–18.7) disability-adjusted life years (DALYs) per 1,000 persons in the third year. Among hospitalized individuals, risk of death declined but remained significantly elevated in the third year after infection (incidence rate ratio: 1.29 (95% CI: 1.19–1.40)). Risk of incident PASC declined over the 3 years, but substantial residual risk remained in the third year, leading to 90.0 (95% CI: 55.2–124.8) DALYs per 1,000 persons. Altogether, our findings show reduction of risks over time, but the burden of mortality and health loss remains in the third year among hospitalized individuals.

Article URL: https://www.nature.com/articles/s41591-024-02987-8

Title

Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection

🤖 Abstract

This research looked at how a person's immune system responds to COVID-19 over time. They studied 165 people who had different levels of sickness from the disease. They found that when people get better quickly, their helper and fighter cells (T cells) that fight the virus come early and are strong. This helps them feel better faster in the hospital. But if T cell responses are weak and take longer to show up, it means someone might end up with a more serious illness later on. They also noticed how antibodies (which are like shields against viruses) form. If they start forming late or not very much, that's linked to having a worse case of COVID-19. Overall, the researchers found out that people who had really bad cases of COVID-19 in the beginning tend to have better protection against getting it again later. This helps us understand how our immune system fights off COVID-19 and may help prevent more waves of infections in the future.

Abstract

The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+and CD8+T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

Article URL: https://www.nature.com/articles/s41392-024-01867-4

Title

Acute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan

🤖 Abstract

The study looked at how people who get sick from the coronavirus (SARS-CoV-2) can have breathing problems later on. They studied two groups of people: one from South Korea and another from Japan. The researchers wanted to see if these people had more trouble breathing after being infected, compared to others who didn't get infected. They found that people who got SARS-CoV-2 were more likely to have breathing issues in the short term (acute respiratory complications) or long-term (post-acute respiratory sequelae) compared to those who didn’t get it. The risk was higher for people with more severe cases of the infection. The study also showed that getting vaccinated against COVID-19 could help reduce these problems. Over time, even though some breathing issues went away, they still existed up to 6 months after someone got infected. Overall, this research helps understand how SARS-CoV-2 can affect people's breathing over time and considers things like vaccination status in making this understanding.

Abstract

Considering the significant burden of post-acute COVID-19 conditions among patients infected with SARS-CoV-2, we aimed to identify the risk of acute respiratory complications or post-acute respiratory sequelae. A binational population-based cohort study was conducted to analyze the risk of acute respiratory complications or post-acute respiratory sequelae after SARS-CoV-2 infection. We used a Korean nationwide claim-based cohort (K-COV-N;n= 2,312,748; main cohort) and a Japanese claim-based cohort (JMDC;n= 3,115,606; replication cohort) after multi-to-one propensity score matching. Among 2,312,748 Korean participants (mean age, 47.2 years [SD, 15.6]; 1,109,708 [48.0%] female), 17.1% (394,598/2,312,748) were infected with SARS-CoV-2. The risk of acute respiratory complications or post-acute respiratory sequelae is significantly increased in people with SARS-CoV-2 infection compared to the general population (acute respiratory complications: HR, 8.06 [95% CI, 6.92-9.38]; post-acute respiratory sequelae: 1.68 [1.62-1.75]), and the risk increased with increasing COVID-19 severity. We identified COVID-19 vaccination as an attenuating factor, showing a protective association against acute or post-acute respiratory conditions. Furthermore, while the excess post-acute risk diminished with time following SARS-CoV-2 infection, it persisted beyond 6 months post-infection. The replication cohort showed a similar pattern in the association. Our study comprehensively evaluates respiratory complications in post-COVID-19 conditions, considering attenuating factors such as vaccination status, post-infection duration, COVID-19 severity, and specific respiratory conditions.

Article URL: https://www.nature.com/articles/s41467-024-48825-w

Title

Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection

🤖 Abstract

The study looked at whether getting a COVID-19 vaccine affected people who already had the virus compared to those who didn't have it. They found that vaccinated people were less likely to get certain health problems after having COVID, especially if they got vaccines from outside doctors. The biggest difference was in skin and blood issues. Even though some small differences still existed, getting a vaccine seemed to help reduce these health problems for most people. This means getting the shot might make it easier to avoid long-term side effects of the virus.

Abstract

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02–1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86–0.95), circulatory (RR: 0.88, 0.83–0.94), blood and hematologic (RR: 0.79, 0.71–0.89), skin and subcutaneous (RR: 0.69, 0.66–0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51–0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1–2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Article URL: https://www.nature.com/articles/s41467-024-48022-9

Title

Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years

🤖 Abstract

Studies looked at how people move around using their phones to see how diseases spread. Before COVID-19, when people visited schools or went to play with kids in their city, they were more likely to get sick from common cold-like viruses that usually stay around all year. After everyone stayed home during the pandemic, these common cold viruses stopped spreading as much. But after restrictions were lifted a bit, where people moved around also affected how SARS-CoV-2 spread. However, this connection became weaker when people started moving around again after new rules went back into place. Overall, changes in how people move seem to matter more for spreading common cold viruses compared to the coronavirus, especially at the start of a disease outbreak.

Abstract

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.

Article URL: https://www.nature.com/articles/s41467-024-48528-2

Title

Dynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19

🤖 Abstract

Different types of COVID-19 viruses kept appearing since the pandemic started. Remdesivir is a medicine used to treat these viruses. But it doesn't work well for people whose immune systems are weak, and they can keep getting sick for a long time. A patient who had trouble breathing because of lung damage caused by another sickness got COVID-19 from the Omicron BA.5 type virus. The virus kept spreading in their body even after treatment with Remdesivir. Scientists found that some changes (mutations) in the virus made it resistant to Remdesivir. One particular mutation, C799F, was very important because it changed a part of the virus that helps the medicine work. This means the medicine couldn't stop the virus anymore. The virus kept changing, with lots of different mutations appearing over time. Because of this, some people who are treated don’t get better and have to deal with resistant viruses that keep them sick for longer.

Abstract

Numerous SARS-CoV-2 variant strains with altered characteristics have emerged since the onset of the COVID-19 pandemic. Remdesivir (RDV), a ribonucleotide analogue inhibitor of viral RNA polymerase, has become a valuable therapeutic agent. However, immunosuppressed hosts may respond inadequately to RDV and develop chronic persistent infections. A patient with respiratory failure caused by interstitial pneumonia, who had undergone transplantation of the left lung, developed COVID-19 caused by Omicron BA.5 strain with persistent chronic viral shedding, showing viral fusogenicity. Genome-wide sequencing analyses revealed the occurrence of several viral mutations after RDV treatment, followed by dynamic changes in the viral populations. The C799F mutation in nsp12 was found to play a pivotal role in conferring RDV resistance, preventing RDV-triphosphate from entering the active site of RNA-dependent RNA polymerase. The occurrence of diverse mutations is a characteristic of SARS-CoV-2, which mutates frequently. Herein, we describe the clinical case of an immunosuppressed host in whom inadequate treatment resulted in highly diverse SARS-CoV-2 mutations that threatened the patient’s health due to the development of drug-resistant variants.

Article URL: https://www.nature.com/articles/s41467-024-47941-x

Title

Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection

🤖 Abstract

This study looks at how people feel immune-wise after having a mild to moderate case of long COVID compared to those who recovered from regular COVID. At 3 months, people with long COVID had higher antibodies against the virus's shell and core than those who fully recovered. They also had more special cells in their body that help fight off the virus for longer periods at 3 and 8 months. By 24 months, these differences didn't last. Some people still had some signs of fighting off the infection, which might mean they were re-infected. But overall, both groups ended up with similar immune responses by then. The study found that people's quality of life improved over time in most cases of long COVID, especially if their levels of a protein called PTX3 or low levels of certain blood markers went down.

Abstract

This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4+T cells, PD-1, and TIM-3 expression on CD4+and CD8+T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.

Article URL: https://www.nature.com/articles/s41467-024-47720-8

Title

SARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals

🤖 Abstract

The study looked at how people's bodies respond after getting a special vaccine called bivalent BA.4/5. Some people had already gotten sick with COVID-19 before. The researchers found that those who hadn't been sick before had bigger reactions to the vaccine, making more antibodies and having stronger protection against different types of coronavirus. However, even those who had been sick still had a good response to the vaccine. The study also showed that people who didn't get sick before were more likely to get infected again after vaccination. This means they had lower levels of protection from their immune system against some specific parts of the virus. In summary, getting vaccinated can still help protect people from COVID-19 even if they've been sick with it before, but those who haven't been sick might not have as strong a response to certain types of viruses.

Abstract

Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n= 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n= 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.

Article URL: https://www.nature.com/articles/s41467-024-47429-8

Title

Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK

🤖 Abstract

The study found that people who had COVID-19 were more likely to develop other health problems like asthma and hay fever later on. This risk increased even more if the COVID-19 was very serious. Getting vaccinated against COVID-19 helped lower this risk a bit. The results held true in different countries with different groups of people, which adds credibility to the findings.

Abstract

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N;n= 836,164; main cohort) and Japan (JMDC;n= 2,541,021; replication cohort A) and the UK Biobank cohort (UKB;n= 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.

Article URL: https://www.nature.com/articles/s41467-024-47176-w

Title

Dynamics of Mpox infection in Nigeria: a systematic review and meta-analysis

🤖 Abstract

Mpox outbreaks happen in parts of West and Central Africa. In Nigeria, many people got sick with it last year. Most cases were from southern Nigeria. We looked at lots of studies about Mpox in Nigeria over almost 50 years. We found that Mpox spread more to northern parts of the country. The main reasons why Mpox spreads are poverty, lack of healthcare, and unsafe sexual practices. Our findings tell us we need to improve healthcare and stop unsafe sex to help stop Mpox spreading.

Abstract

The seasonal outbreaks of Mpox continue in most parts of West and Central Africa. In the past year, Nigeria had the highest number of reported cases. Here, we used the PRISMA guidelines to carry out a systematic review and meta-analysis of available evidence on Mpox in Nigeria to assess the prevalence, transmission pattern, diagnostic approach, and other associated factors useful for mitigating the transmission of the disease. All relevant observational studies in PubMed/MEDLINE, Embase, AJOL, Web of Science, Scopus and Google Scholar on Mpox in Nigeria were assessed within the last fifty years (1972 to 2022). In all, 92 relevant articles were retrieved, out of which 23 were included in the final qualitative analysis. Notably, most of the cases of Mpox in Nigeria were from the southern part of the country. Our findings showed a progressive spread from the southern to the northern region of the country. We identified the following factors as important in the transmission of Mpox in Nigeria; poverty, lack of basic healthcare facilities, and risk of exposure through unsafe sexual practices. Our findings reiterate the need to strengthen and expand existing efforts as well as establish robust multi-sectoral collaboration to understand the dynamics of Mpox Nigeria.

Article URL: https://www.nature.com/articles/s41598-024-58147-y

Title

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses

🤖 Abstract

This abstract talks about making special medicine to fight poxviruses, which can make people very sick. Right now, it's hard and expensive to create these medicines. But scientists found a new way using tiny messenger molecules called mRNA, put inside little fat particles called liposomes. They made different mixtures of these mRNA messages that tell the body how to make special antibodies that fight poxviruses. When they tested this on mice, the mice didn't get sick as badly when given these mRNA messages. One mixture of these messages helped protect against all types of poxviruses. The scientists think this could be a good way to create medicines for other viruses too.

Abstract

TheOrthopoxvirusgenus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Article URL: https://www.nature.com/articles/s41392-024-01766-8

Title

Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-naïve adults receiving the first four mRNA COVID-19 vaccine doses

🤖 Abstract

This study looked at how a series of vaccine shots affects the body's ability to make antibodies against COVID-19 in people who have never had it before. They gave different groups of people either one, two, three, or four shots. Blood samples were taken from them both before and after each shot was given. They found that: - People who got the mRNA-1273 vaccine made more antibodies. - Men made more antibodies than women. - Younger people made more antibodies than older ones. - People who didn't smoke had higher antibody levels. - Those with no medicines to suppress their immune system also had higher levels. They noticed that: - The longer it was since they got their last shot, the more antibodies they made. - Getting a second shot after an initial one always resulted in better results. These findings can help make vaccination plans better.

Abstract

To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Article URL: https://www.nature.com/articles/s41598-024-57931-0

Title

Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population

🤖 Abstract

Despite some people getting sick from COVID-19, they might later have problems like anxiety or mood issues. Studies showed that people who got infected had a higher chance of developing these mental health issues compared to those who didn't get infected. People who were hospitalized were even more likely to develop these problems. Vaccines seemed to help protect against some of these mental health issues, though not completely. Getting the vaccine still meant there was a risk, just less than for people who weren’t vaccinated at all or only got part of the vaccine. It's important to catch and treat mental health issues early in COVID survivors, especially those who were very sick or didn't get vaccinated. As more people get infected without getting vaccinated (called "breakthrough infections"), we need better ways to prevent serious mental health problems from developing.

Abstract

Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n= 26,101), contemporary control with no evidence of infection (n= 380,337) and historical control predating the pandemic (n= 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42–1.67;P= 1.70 × 10−24; difference in incidence rate: 27.36, 95% CI 21.16–34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70–2.78;P= 5.80 × 10−10) than those not hospitalized (1.41, 1.30–1.53;P= 1.46 × 10−16), and were reduced in fully vaccinated people (0.97, 0.80–1.19;P= 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49–1.79;P= 4.95 × 10−26). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78–1.07;P= 0.278) but increased prescription risk (1.42, 1.00–2.02;P= 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.

Article URL: https://www.nature.com/articles/s41562-024-01853-4

Title

Neurofilament light chain and glial fibrillary acid protein levels are elevated in post-mild COVID-19 or asymptomatic SARS-CoV-2 cases

🤖 Abstract

The COVID-19 pandemic caused brain problems in some people who had mild or no symptoms before. To see how well their brains were working now that the virus was gone, researchers looked at two substances in their blood: NF-L and GFAP. These substances can show if someone's brain cells are getting damaged. They studied 147 grown-ups who used to have COVID-19 but didn't know they did or had very mild symptoms. They also checked some people without any illness nearby, like how the grown-up group is similar to them in age and body size. The researchers found that the grown-ups with brain problems had more of these substances in their blood compared to those who were healthy. Also, after checking again after about a year, even though they still had higher levels, it was less than what healthy people have. This shows that sometimes, when the virus is gone, parts of someone's brain can be damaged, but over time, this damage gets better.

Abstract

Given the huge impact of the COVID-19 pandemic, it appears of paramount importance to assess the cognitive effects on the population returning to work after COVID-19 resolution. Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) represent promising biomarkers of neuro-axonal damage and astrocytic activation. In this cohort study, we explored the association between sNfL and sGFAP concentrations and cognitive performance in a group of 147 adult workers with a previous asymptomatic SARS-CoV-2 infection or mild COVID-19, one week and, in 49 of them, ten months after SARS-Cov2 negativization and compared them to a group of 82 age and BMI-matched healthy controls (HCs). sNfL and sGFAP concentrations were assessed using SimoaTM assay Neurology 2-Plex B Kit. COVID-19 patients were interviewed one-on-one by trained physicians and had to complete a list of questionnaires, including the Cognitive Failure Questionnaire (CFQ). At the first assessment (T0), sNfL and sGFAP levels were significantly higher in COVID-19 patients than in HCs (p < 0.001 for both). The eleven COVID-19 patients with cognitive impairment had significantly higher levels of sNfL and sGFAP than the others (p = 0.005 for both). At the subsequent follow-up (T1), sNfL and sGFAP levels showed a significant decrease (median sNfL 18.3 pg/mL; median sGFAP 77.2 pg/mL), although they were still higher than HCs (median sNfL 7.2 pg/mL, median sGFAP 63.5 pg/mL). Our results suggest an ongoing damage involving neurons and astrocytes after SARS-Cov2 negativization, which reduce after ten months even if still evident compared to HCs.

Article URL: https://www.nature.com/articles/s41598-024-57093-z

Title

Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants

🤖 Abstract

The abstract talks about whether tiny bits of air carrying coronavirus (called aerosols) can still make people sick. Some researchers think these bits are dangerous, but others aren't sure. So we did tests to see if these aerosols could have the virus that causes COVID-19 and how many people had them. We found out that for some types of test results from people who had the virus, about half or more of those people were likely spreading the virus in their air. People with lower protection against the virus in their bodies seemed to be better at making these spreadable bits of air. The study also found a quick way to guess whether someone is likely to make these dangerous bits of air - just by looking at some parts of their blood. What this means is that we now know more about how and who spreads coronavirus through the air, which can help us stop it better in the future.

Abstract

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10μm and <5μm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5μm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

Article URL: https://www.nature.com/articles/s41467-024-45400-1

Title

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection

🤖 Abstract

This study looked at people who got infected with the coronavirus (SARS-Co-V-2) and compared them to those who didn't get infected, focusing on how vaccination affects their health over time in Hong Kong. They found that getting vaccinated or having a booster shot reduces the risk of long-term health problems like heart issues and death after being sick from COVID for about a year. Unvaccinated people had higher risks even months later. The study shows vaccines help prevent serious health effects from the virus.

Abstract

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Article URL: https://www.nature.com/articles/s41467-024-45953-1

Title

SARS-CoV-2 infection status in corneal preservation solution and COVID-19 prevalence after corneal transplantation

🤖 Abstract

The study found that corneas from COVID-19-infected donors did not have the virus inside them. They tested 144 cornea transplants and found no signs of COVID-19 infection. All the patients who got new corneas were healthy after surgery, even though they had to take steroid medicine for a long time. The research suggests testing for COVID-19 in donors' throats before giving them corneas can help prevent infections in people who get new eyes.

Abstract

The potential risks associated with organs from COVID-19-infected donors were unclear. To determine the SARS-CoV-2 infection status of corneas transplanted during the COVID-19 pandemic, we performed a polymerase chain reaction (PCR) using the corneal preservation solution that was used for corneal transplantation. We also examined the postoperative health status of the recipients. This study included 144 transplants in 143 eyes. Ninety-nine eyes of imported corneas and 10 of the 14 corneas donated in the prefecture were PCR tested at our hospital, and all were SARS-CoV-2 negative. All corneal transplants were performed after confirming their SARS-CoV-2 negativity by a PCR using a corneal preservation solution at our hospital or a nasopharyngeal swab at a previous facility. Despite postoperative steroid administration, no patient developed COVID-19 infection until discharge. Hence, if the donor's nasopharyngeal swab test is SARS-CoV-2 negative, COVID-19 infection in the recipient due to corneal transplantation may be prevented. Since corneal transplant recipients are susceptible to infection due to prolonged steroid administration and are at high risk for severe diseases if infection occurs, SARS-CoV-2 detection testing using nasopharyngeal swabs in donors should be performed.

Article URL: https://www.nature.com/articles/s41598-024-53863-x

Title

SARS-CoV-2 vaccination may mitigate dysregulation of IL-1/IL-18 and gastrointestinal symptoms of the post-COVID-19 condition

🤖 Abstract

The vaccine helped prevent serious illness from the coronavirus. Some people who had the virus still get sick after recovery, called post-COVID conditions (PCC). Researchers looked at how well the vaccine worked for those with PCC and found that getting vaccinated might help reduce certain symptoms like stomach problems. People who didn't have any of these issues before vaccination showed no signs of improvement. But people with PCC who got vaccinated had lower levels of two proteins in their blood, which might mean fewer stomach troubles.

Abstract

The rapid development of safe and effective vaccines helped to prevent severe disease courses after SARS-CoV-2 infection and to mitigate the progression of the COVID-19 pandemic. While there is evidence that vaccination may reduce the risk of developing post-COVID-19 conditions (PCC), this effect may depend on the viral variant. Therapeutic effects of post-infection vaccination have been discussed but the data for individuals with PCC remains inconclusive. In addition, extremely rare side effects after SARS-CoV-2 vaccination may resemble the heterogeneous PCC phenotype. Here, we analyze the plasma levels of 25 cytokines and SARS-CoV-2 directed antibodies in 540 individuals with or without PCC relative to one or two mRNA-based COVID-19 vaccinations as well as in 20 uninfected individuals one month after their initial mRNA-based COVID-19 vaccination. While none of the SARS-CoV-2 naïve individuals reported any persisting sequelae or exhibited PCC-like dysregulation of plasma cytokines, we detected lower levels of IL-1β and IL-18 in patients with ongoing PCC who received one or two vaccinations at a median of six months after infection as compared to unvaccinated PCC patients. This reduction correlated with less frequent reporting of persisting gastrointestinal symptoms. These data suggest that post-infection vaccination in patients with PCC might be beneficial in a subgroup of individuals displaying gastrointestinal symptoms.

Article URL: https://www.nature.com/articles/s41541-024-00815-1

Title

Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study

🤖 Abstract

The study found that babies exposed in the womb to someone sick with coronavirus had more breathing problems, especially if their mom wasn't vaccinated. The researchers looked at moms who got infected while pregnant and compared them to moms who were vaccinated before getting sick. They also checked how the baby's body reacted to the virus. Babies without a vaccine from their mom had twice as much trouble breathing than babies whose moms got vaccinated first. This was because of problems with tiny hair-like things in the lungs that help move air, and the baby making more antibodies (IgE) which can sometimes cause inflammation. Vaccinating moms before they get infected seems to lower how often this happens in their babies.

Abstract

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD followingin uteroexposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.

Article URL: https://www.nature.com/articles/s41467-023-44549-5

Title

Estimating the heritability of SARS-CoV-2 susceptibility and COVID-19 severity

🤖 Abstract

SARS-CoV-2 has infected over 340 million people. Scientists want to find ways to treat COVID-19. Genetic studies can show where drugs might work better. But we also need to understand if some people are more likely to get sick or have worse symptoms because of their genes. Research shows that genetics explain about 1.2% and 5.8% of why some people are more susceptible (can catch it easily) or have a worse condition when they do get sick. Some research used families' genetic information to look at these numbers better. They found that for susceptibility, the genes explained between 33% and 70% of cases. For how long someone is hospitalized with COVID-19, genetics accounted for about 41%. Scientists think both genes and things in their environment (like if they had a clean place to live) help cause these differences. But what people inherited from their parents seems to matter more when it comes to getting sick. During the pandemic, as vaccines came out, how much of why some people got sick was due to genetics changed. It's hard for scientists to understand all this during such big changes in health habits and medical care.

Abstract

SARS-CoV-2 has infected over 340 million people, prompting therapeutic research. While genetic studies can highlight potential drug targets, understanding the heritability of SARS-CoV-2 susceptibility and COVID-19 severity can contextualize their results. To date, loci from meta-analyses explain 1.2% and 5.8% of variation in susceptibility and severity respectively. Here we estimate the importance of shared environment and additive genetic variation to SARS-CoV-2 susceptibility and COVID-19 severity using pedigree data, PCR results, and hospitalization information. The relative importance of genetics and shared environment for susceptibility shifted during the study, with heritability ranging from 33% (95% CI: 20%-46%) to 70% (95% CI: 63%-74%). Heritability was greater for days hospitalized with COVID-19 (41%, 95% CI: 33%-57%) compared to shared environment (33%, 95% CI: 24%-38%). While our estimates suggest these genetic architectures are not fully understood, the shift in susceptibility estimates highlights the challenge of estimation during a pandemic, given environmental fluctuations and vaccine introduction.

Article URL: https://www.nature.com/articles/s41467-023-44250-7

Title

Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study

🤖 Abstract

Post-COVID-19 syndrome is a big health issue. We studied 590 people who got sick from COVID-19 after they left the hospital, tracking their recovery for a year. We found four groups based on how badly different parts of their bodies were affected: 1. Minimal: Not much hurt. 2. Physical: Lots of trouble moving around and feeling tired. 3. Mental/Cognitive: Problems with thinking and memory. 4. Multidomain: A mix of all the above problems. Women got more of these problems, and some people had other health issues too. When people were first sick: - If they had lots of the virus in their lungs, - If they didn't have good antibodies to fight it, - Or if they had fewer special immune cells called B lymphocytes, They often ended up in one of those groups. People who had problems with thinking and memory had higher levels of a chemical called FGF21 in their blood. Those with physical issues did too, but also had higher levels of FGF21 overall. This information could help doctors figure out better ways to treat or prevent Post-COVID-19 syndrome in the future.

Abstract

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.

Article URL: https://www.nature.com/articles/s41467-023-44090-5

Title

Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection

🤖 Abstract

This study found many previously unknown ways that a person's body can fight off the coronavirus (SARS-CoV-2). They used experiments with CRISPR, which is like a gene scissors, to look at what parts of our bodies are important for fighting viruses. They looked at how different cells work together and interact with viruses. They discovered several new parts of our body that help stop the virus from entering or growing inside us. These include parts of the V-ATPases, ESCRT, N-glycosylation pathways, which are like different tools in a toolbox for fighting off viruses. They also found out about an important group called cohesin complex and another part called KLF5 that helps fight the virus. The KLF5 is special because it's related to something we eat - things called sphingolipids. The study showed how removing these parts can make cells more vulnerable to getting sick from COVID-19, especially in severe cases. This research could help find new ways to protect people from getting worse with the virus.

Abstract

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discover another anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which is up-regulated, and harbors genetic variations linked to COVID-19 patients with severe symptoms. Anti-viral effects of three identified candidates (DAZAP2/VTA1/KLF5) are confirmed individually. Molecular characterization of DAZAP2/VTA1/KLF5-knockout cells highlights the involvement of genes related to the coagulation system in determining the severity of COVID-19. Together, our results provide further resources for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.

Article URL: https://www.nature.com/articles/s41467-023-44175-1

Title

Neutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children

🤖 Abstract

The study looked at how well different vaccines work against new coronavirus strains in children. They found that after getting infected or vaccinated, kids don't make strong enough antibodies to fight off some of the new Omicron subtypes like BQ.1, BQ.1.1, and XBB.1. This means current vaccines might not be as effective against these variants. The research suggests we need better vaccines that can protect children from these new strains more effectively.

Abstract

Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5–11, 12–21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children.

Article URL: https://www.nature.com/articles/s41467-023-43152-y

Title

Infectivity of exhaled SARS-CoV-2 aerosols is sufficient to transmit covid-19 within minutes

🤖 Abstract

The study found that when people start feeling sick with COVID-19, tiny droplets of their breath (called aerosols) carry the virus. These droplets are released into the air and spread the disease very easily. The researchers measured how many of these droplets contain enough of the virus to make someone sick. They looked at three different people and found that singing releases the most droplets with the virus inside them. One person coughed out 4 TCID50 per second, another one exhaled 36 per second, and the third person let out 127 per second. The researchers used a computer model to guess what would happen if someone who had just caught COVID-19 came into a room where people were walking around normally. They found that in about 6 minutes to less than an hour, someone could breathe in enough droplets carrying the virus to become sick themselves. So basically, the study shows that when someone with COVID-19 is singing or breathing heavily, they can spread the disease very quickly and easily in a regular room where people are moving around.

Abstract

Exhaled SARS-CoV-2-containing aerosols contributed significantly to the rapid and vast spread of covid-19. However, quantitative experimental data on the infectivity of such aerosols is missing. Here, we quantified emission rates of infectious viruses in exhaled aerosol from individuals within their first days after symptom onset from covid-19. Six aerosol samples from three individuals were culturable, of which five were successfully quantified using TCID50. The source strength of the three individuals was highest during singing, when they exhaled 4, 36, or 127 TCID50/s, respectively. Calculations with an indoor air transmission model showed that if an infected individual with this emission rate entered a room, a susceptible person would inhale an infectious dose within 6 to 37 min in a room with normal ventilation. Thus, our data show that exhaled aerosols from a single person can transmit covid-19 to others within minutes at normal indoor conditions.

Article URL: https://www.nature.com/articles/s41598-023-47829-8

Title

The burden of post-acute COVID-19 symptoms in a multinational network cohort analysis

🤖 Abstract

This study looked at people who had gotten sick from COVID-19 and how many still felt bad for months afterward. They studied lots of people in Spain and the UK. They found that as time went on, fewer people were feeling sick after their initial illness. But even those with only one case of COVID often had trouble with smell and taste for a long time. People who got sick again (re-infected) had more lingering symptoms than those who got only one infection. The researchers think there might be different ways to define "long COVID" and they suggest people need more research to find better treatments.

Abstract

Persistent symptoms following the acute phase of COVID-19 present a major burden to both the affected and the wider community. We conducted a cohort study including over 856,840 first COVID-19 cases, 72,422 re-infections and more than 3.1 million first negative-test controls from primary care electronic health records from Spain and the UK (Sept 2020 to Jan 2022 (UK)/March 2022 (Spain)). We characterised post-acute COVID-19 symptoms and identified key symptoms associated with persistent disease. We estimated incidence rates of persisting symptoms in the general population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential by comparing their frequency in COVID-19 cases vs. matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections.Our study shows that the proportion of COVID-19 cases affected by persistent post-acute COVID-19 symptoms declined over the study period. Risk for altered smell/taste was consistently higher in patients with COVID-19 vs test-negative controls. Persistent symptoms were more common after reinfection than following a first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms.

Article URL: https://www.nature.com/articles/s41467-023-42726-0

Title

A hybrid register and questionnaire study of Covid-19 and post-acute sick leave in Denmark

🤖 Abstract

Post-acute sick leave means how people feel sick after they recover from the flu-like illness caused by a virus called SARS-CoV-2. We did a survey where many people said if they had to stay home because they were very sick. The study found that more women, especially those in their 50s and 60s, as well as those with certain health problems like lung issues or being extra heavy (obesity), took longer to get back to feeling normal after the flu-like illness. These findings might help doctors make better ways to diagnose and treat people who still feel sick months later.

Abstract

Post-acute sick leave is an underexplored indicator of the societal burden of SARS-CoV-2. Here,  we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which include 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index- and alpha-dominant waves. We observe that an additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave is defined as >1 month of sick leave within the period 1–9 months after the RT-PCR test date. Being female, 50–65 years, or having certain pre-existing health conditions such as obesity, chronic lung diseases, and fibromyalgia each increase risk for taking substantial sick leave. Altogether, these results may help motivate improved diagnostic and treatment options for persons living with post-Covid conditions.

Article URL: https://www.nature.com/articles/s41467-023-42048-1

Title

Retinal vascular occlusion risks during the COVID-19 pandemic and after SARS-CoV-2 infection

🤖 Abstract

This study looked at how many people developed problems with their eye blood vessels, like clots, before and during a time when lots of people had coronavirus (COVID-19). They compared the number of these problems in two groups: those who tested positive for COVID-19 and those suspected to have it. The researchers found that having COVID-19 did not make people more likely to get blood vessel issues in their eyes, though they saw a small drop in one kind of problem (retinal vein occlusion) and an increase in another (retinal artery occlusion) during the pandemic.

Abstract

The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018–2019 and 2020–July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018–2019 and 2020–2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018–2019 and 2020–2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence.

Article URL: https://www.nature.com/articles/s41598-023-44199-z

Title

Self-sampling monkeypox virus testing in high-risk populations, asymptomatic or with unrecognized Mpox, in Spain

🤖 Abstract

A group studied how the monkeypox virus (MPXV) affects gay, bisexual men, trans women, and non-binary people who don't show symptoms or might have missed getting sick from MPXV. They took swabs from their bottom parts to test for the virus using a new method. Out of 113 participants, 7 had MPXV in their samples (about 6%). Most weren’t showing any signs they were infected but some showed no symptoms and still tested positive. The study found that not all people who have it show obvious sickness, which means checking only for known symptoms might miss some cases of the virus. This shows we need better ways to catch everyone who has MPXV.

Abstract

The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0–43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%–10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.

Article URL: https://www.nature.com/articles/s41467-023-40490-9

Title

Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome

🤖 Abstract

The Epstein-Barr virus and other viruses can cause symptoms after a person recovers from COVID-19. This study looked at how vaccines might help reduce these lingering symptoms. Researchers checked if people with long-COVID had more or fewer of certain viruses like parvovirus and Herpesviridae. They also saw if getting vaccinated against COVID-19 helped lessen the effects of those other viruses in patients who still felt sick after recovering from a full-blown case of COVID-19. They found that people who got vaccinated had fewer symptoms overall, less of these virus-related antibodies in their blood, and lower levels of certain types of antibodies related to Herpesviridae. This suggests that getting the COVID-19 vaccine might help reduce lingering symptoms by stopping some of these viruses from fighting each other inside the body. So basically, vaccines could be helping prevent other viruses from causing more problems after someone gets better from COVID-19.

Abstract

Epstein–Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021–May 2022 (median 243 days post-COVID-19 infection). DNA virus–related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p< 0.001), significantly less cumulative DNA virus–related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).

Article URL: https://www.nature.com/articles/s41541-023-00739-2