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167 lines
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<title>13 January, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease</strong> -
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<div>
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Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Integration of COVID-19 patient data with two hamster models that develop moderate (Syrian hamster, Mesocricetus auratus) or severe (Roborovski hamster, Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and severe COVID-19 patients, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Consistently, hamster's response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.574849v1" target="_blank">Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease</a>
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</div></li>
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<li><strong>Investigating willingness to share autonomous shuttles with strangers: The mediating effects of trust and optimism</strong> -
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<div>
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If autonomous vehicles are to have beneficial impacts on society, people must be willing to use them in their everyday lives. Many studies have engaged in questions regarding the technology of automation and how drivers will interact with it. However, little research has focused on the social situation arising from small shared autonomous shuttles (SASs) used in public transportation. This study aims to investigate a conceptual framework suggested by previous research and the MAVA-model. We tested a conceptual model where the background variables’ impact is mediated through trust in SASs and technology optimism. Our two dependent variables were the intention to use SASs with strangers without a steward onboard and the importance of social distance. The current article uses data collected using two identical online surveys conducted in 2020 (n=922) and 2021 (n=608). The data were collected before and after a pilot using SAS was employed in a suburban area outside Oslo. Examining the same population before and after the pilot gives us crucial insight into the development of attitudes toward automated vehicles when exposed to them in regular traffic. We find that trust in SASs and technological optimism positively predict willingness to use SAS. However, the passage of time had a negative effect on trust and tech-optimism, which in turn lowered the intentions to use. The background variables have little effect on the mediators. Contrary to previous research, we find that familiarity with the pilots predicted lower technological optimism and thus lower intentions to use. Older participants and women reported less trust in SASs and less tech-optimism compared to others. In the next step, these mediators lowered the intention to use SASs. These two groups also feel that it is more important to be able to keep social distance while riding SASs. The participants who use active transport modes think it is less important with social distance. The ongoing COVID-19 pandemic may also impact the results. The proposed model was less suited for predicting desire for social distance than for intentions to use. Our results suggest that future pilots should take care not to leave a negative impression by employing immature technology in neighborhoods, as this may be detrimental to the perception of SASs. Furthermore, transportation providers should take care to meet the social needs of exposed groups in the novel social context created by SASs.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/x4v3h/" target="_blank">Investigating willingness to share autonomous shuttles with strangers: The mediating effects of trust and optimism</a>
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</div></li>
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<li><strong>Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</strong> -
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<div>
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Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1- deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527147v3" target="_blank">Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</a>
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</div></li>
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<li><strong>Science knowledge and trust in medicine affect individuals’ behavior in pandemic crises</strong> -
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<div>
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In pandemic crises such as the COVID-19 pandemic, individuals’ behavior has a strong impact on epidemiological processes. Compliance with prevention guidelines, such as social distancing, is critical to avoid further spreading an infectious disease or to slow down its spread. However, some individuals also or instead engage in panic behavior, such as hoarding. We investigate how education prepares individuals to respond adequately by modelling the path from seeking information about COVID-19 to eventual behavior. Based on a sample of N = 1,182 adult Americans, gathered at the pandemic’s onset (March 2020), we conclude that science knowledge helps individuals convert information into coronavirus knowledge. This knowledge then helps individuals avoid panic behavior. Individuals lacking coronavirus knowledge and science knowledge still comply with prevention guidelines when they have a general trust in medicine. Individuals lacking knowledge still follow prevention guidelines when they trust in medicine. Facilitating science knowledge and trust in science through education and targeted public health messaging are likely to be of fundamental importance for bringing crises such as the 2020 COVID-19 pandemic under control.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/tmu8f/" target="_blank">Science knowledge and trust in medicine affect individuals’ behavior in pandemic crises</a>
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</div></li>
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<li><strong>Individual Psychological Responses to the SARS-CoV-2 Pandemic: Different Clusters and Their Relation to Risk-Reducing Behavior</strong> -
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<div>
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Understanding individual difference in psychological responses toward the Coronavirus (SARS-CoV-2) crisis is essential to the adequate handling of the current pandemic. Based on a sample of 1,182 American adult residents (stratified for age and gender; data collection March 13 to 15, 2020), we found three distinct clusters of psychological responses (i.e., informed, panic, and ignorant). Clusters differed regarding their knowledge about the virus, SARS-CoV-2-related anxiety (i.e., worry and emotionality), and evaluation of the SARS-CoV-2 crisis’s severity. Cluster membership was strongly associated with both SARS-CoV-2 risk-reducing, reasonable behavior and unreasonable behavior. Finally, clusters could be linked to systematic differences in broader personality dimensions (i.e., Dark Triad and Big Five). Our study provides and validates a set of clusters of individual psychological responses to the SARS-CoV-2 pandemic and the resulting behavior. It functions as a pivotal starting point for longitudinal observations on the effectiveness of public health communications in this global challenge.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/k8unc/" target="_blank">Individual Psychological Responses to the SARS-CoV-2 Pandemic: Different Clusters and Their Relation to Risk-Reducing Behavior</a>
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</div></li>
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<li><strong>APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19</strong> -
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<div>
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Motivation: Computational analyses of plasma proteomics provide translational insights into complex diseases such as COVID-19 by revealing molecules, cellular phenotypes, and signaling patterns that contribute to unfavorable clinical outcomes. Current in silico approaches dovetail differential expression, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking. Results: We introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically-informed sparse deep learning model to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests co-expression and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19. Availability and Implementation: APNet R, Python scripts and Cytoscape methodologies are available at https://github.com/BiodataAnalysisGroup/APNet Contact: ggeorav@certh.gr Supplementary information: Supplementary information can be accessed in Zenodo (10.5281/zenodo.10438830).
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.575161v1" target="_blank">APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19</a>
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</div></li>
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<li><strong>SARS-CoV-2 papain-like protease activates nociceptors to drive sneeze and pain</strong> -
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<div>
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SARS-CoV-2, the virus responsible for COVID-19, triggers symptoms such as sneezing, aches and pain. These symptoms are mediated by a subset of sensory neurons, known as nociceptors, that detect noxious stimuli, densely innervate the airway epithelium, and interact with airway resident epithelial and immune cells. However, the mechanisms by which viral infection activates these neurons to trigger pain and airway reflexes are unknown. Here, we show that the coronavirus papain-like protease (PLpro) directly activates airway-innervating trigeminal and vagal nociceptors in mice and human iPSC-derived nociceptors. PLpro elicits sneezing and acute pain in mice and triggers the release of neuropeptide calcitonin gene-related peptide (CGRP) from airway afferents. We find that PLpro-induced sneeze and pain requires the host TRPA1 ion channel that has been previously demonstrated to mediate pain, cough, and airway inflammation. Our findings are the first demonstration of a viral product that directly activates sensory neurons to trigger pain and airway reflexes and highlight a new role for PLpro and nociceptors in COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.10.575114v1" target="_blank">SARS-CoV-2 papain-like protease activates nociceptors to drive sneeze and pain</a>
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</div></li>
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<li><strong>Depression and fatigue six months post-COVID-19 disease are associated with overlapping symptom constellations: A prospective, multi-centre, population-based cohort study</strong> -
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<div>
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Background: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. Methods. To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data was collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from more than 2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. Results. Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. Limitations. The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometrically collected data. Conclusions. In summary, our results suggest a strong link between post-COVID depression and fatigue and thus highlighting the need for integrative treatment approaches.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/bjr6n/" target="_blank">Depression and fatigue six months post-COVID-19 disease are associated with overlapping symptom constellations: A prospective, multi-centre, population-based cohort study</a>
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</div></li>
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<li><strong>Case study on policies in response to COVID-19</strong> -
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<div>
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This report assesses the response policies pursued during the COVID-19 pandemic in six countries: Belgium, Croatia, Poland, Spain, Sweden, and the United Kingdom. The analysis covers the first year of the pandemic (2020 – 2021), including 2022 when possible. Examining the impact on families, particularly in income protection, care policies, and work-life balance, the analysis focus on the unique challenges families faced during prolonged lockdowns and States of Emergency. Resilience, shaped by resources within families, communities, or national welfare systems, becomes a focal point. Whilst community cooperation was widespread, the study concentrates exclusively on national-level policy responses. The pandemic disproportionately affected vulnerable individuals and families, with pre-existing economic conditions and societal readiness at play. A crucial aspect is the potential trade-off between health protection and individual autonomy which, modulated by the welfare state, suggests a delicate balance between protection and personal freedom. In contrast to the austerity measures in 2008, governments introduced diverse mechanisms during the pandemic to protect incomes and jobs. Job Replacement Schemes prevented mass employment destruction, while social policies acted as a ‘social shield’ against poverty risks. All European states increased control over health systems, hospitals, and the economy, emphasizing the pivotal role of welfare states in interventions. The increased authority of states also led to temporary interventions fostering social policy innovation. Despite shared goals, countries adopted diverse strategies across the three policy areas in our study. Concerning income protection, those with stronger and more inclusive welfare states required fewer additional measures, illustrated by the broader relief measures implemented by the United Kingdom and Croatia. Some countries enhanced their existing minimum income programs, whereas others launched new ones, such as Spain’s national minimum income scheme. In the realm of childcare services and education closures, most countries prioritized key workers’ children during the pandemic. Sweden was the exception, keeping the centres open to all. Parental and care leaves were also crucial for managing work-family balance, with Sweden, Belgium, and Poland introducing more inclusive policies than Spain. Finally, protection measures for older individuals aimed at enhancing access to personal protective equipment, testing, and isolation measures revealed shared priorities and variations in policy execution. Our findings show that welfare states, traditionally confined by limits, stretched their protective sphere beyond usual boundaries during the pandemic, acting as crucial economic stabilizers and social cohesion devices. The report underscores the role of the welfare state as a ‘risk absorber’, highlighting that inclusive and generous welfare states provide additional protection within existing frameworks. Particularly, anti-poverty policies like minimum income schemes prove more effective in addressing pandemic-induced vulnerabilities than weaker or less-funded interventions. Central concepts of inclusivity, flexibility, and complementarity stress the importance of social policy’s adaptability and consistency across domains. Overall, social protection systems embodying these traits seem better equipped to confront unforeseen risks amid the complex and volatile nature of the pandemic times. The long-term implications for welfare state reform remain uncertain, but the pandemic showcased both the limits and the adaptive capacity of welfare states in the face of unprecedented challenges.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/z783a/" target="_blank">Case study on policies in response to COVID-19</a>
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<li><strong>The impact of COVID-19 on the debate on open science: An analysis of expert opinion</strong> -
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<div>
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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.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/xy874/" target="_blank">The impact of COVID-19 on the debate on open science: An analysis of expert opinion</a>
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<li><strong>Inequality and Immigration Do Not Necessarily Increase Welfare Chauvinism – A Replication of Two Influential Studies</strong> -
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<div>
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How do inequality and immigration affect support for redistribution? We study this question in light of the Covid-19 pandemic, which has elevated the salience of redistributive policies and decreased the salience of immigration. We build upon studies of Magni (2021) and Alesina, Miano and Stantcheva (2023) that showed that priming respondents on inequality or immigration can link to preferences for redistribution (the former positively, the latter negatively) and increase welfare chauvinism. We revisit these claims drawing on survey-experimental primes in a quota-representative sample of around (N=1.587) German citizens. Our findings are partly contrary to prior evidence, underlining that previous studies may be context-dependent on times of exceptionally high immigration salience.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nt8c4/" target="_blank">Inequality and Immigration Do Not Necessarily Increase Welfare Chauvinism – A Replication of Two Influential Studies</a>
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<li><strong>Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy to treat murine liver diseases</strong> -
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<div>
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Primary human hepatocyte (PHH) transplantation is a promising alternative to liver transplantation, whereby liver function could be restored by partial repopulation of the diseased organ with healthy cells. However, currently PHH engraftment efficiency is low and benefits are not maintained long-term. Here we refine two mouse models of human chronic and acute liver diseases to recapitulate compromised hepatocyte proliferation observed in nearly all human liver diseases by overexpression of p21 in hepatocytes. In these clinically relevant contexts, we demonstrate that transient, yet robust expression of human hepatocyte growth factor and epidermal growth factor in the liver via nucleoside-modified mRNA in lipid nanoparticles, whose safety was validated with mRNA-based COVID-19 vaccines, drastically improves PHH engraftment, reduces disease burden, and improves overall liver function. This novel strategy may overcome the critical barriers to clinical translation of cell therapies with primary or stem cell-derived hepatocytes for the treatment of liver diseases.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.575286v1" target="_blank">Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy to treat murine liver diseases</a>
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<li><strong>Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics</strong> -
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<div>
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The worldwide spread of SARS-CoV-2 has been characterised by the emergence of several variants of concern (VOCs) presenting an increasing number of mutations in the viral genome. The spike glycoprotein, responsible for engaging the viral receptor ACE2, exhibits the highest density of mutations, suggesting an ongoing evolution to optimize viral entry. However, previous studies focussed on isolated molecular interactions, neglecting the intricate composition of the plasma membrane and the interplay between viral attachment factors. Our study explores the role of avidity and of the complexity of the plasma membrane composition in modulating the virus-host binding kinetics during the early stages of viral entry for the original Wuhan strain and three VOCs: Omicron BA.1, Delta, and Alpha. We employ fluorescent liposomes decorated with spike from several VOCs as virion mimics in single-particle tracking studies on native supported lipid bilayers derived from pulmonary Calu-3 cells. Our findings reveal an increase in the affinity of the multivalent bond to the cell surface for Omicron driven by an increased association rate. We show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed on cells’ plasma membrane, plays a central role in modulating the interaction with the cell surface and we observe a shift in its role from screening the interaction with ACE2 in early VOCs to an important binding factor for Omicron. This is caused by a ~10-fold increase in Omicron’s affinity to HS compared to the original Wuhan strain, as shown using atomic force microscopy-based single-molecule force spectroscopy. Our results show the importance of coreceptors, particularly HS, and membrane complexity in the modulation of the attachment in SARS-CoV-2 VOCs. We highlight a transition in the variants’ attachment strategy towards the use of HS as an initial docking site, which likely plays a role in shaping Omicron’s tropism towards infection of the upper airways, milder symptoms, and higher transmissibility.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.10.574981v1" target="_blank">Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics</a>
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<li><strong>Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice</strong> -
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<div>
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The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as Post-COVID syndrome (PCS). Current estimates suggest that more than 65 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10^3 to 3x105 PFU/30 uL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10^4 PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and were prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.10.575003v1" target="_blank">Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice</a>
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<li><strong>Effective assessment of CD4+ T cell Immunodominance patterns: impact of antigen processing and HLA restriction</strong> -
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Identifying T cell epitopes is essential for studying and potentially tuning immune responses to pathogens. The polymorphic nature of major histocompatibility complex of class II (MHCII)-genes, and the complexity of the antigen processing mechanisms hinders the effective prediction of immunodominant patterns in humans, specially at the population level. Here, we combined the output of a reconstituted antigen processing system and of in silico prediction tools for SARS-CoV-2 antigens considering a broad-population coverage DRB1* panel to gain insights on immunodominance patterns. The two methods complement each other, and the resulting model improves upon single positive predictive values (PPV) from each of them to explain known epitopes. This model was used to design a minimalistic peptide pool (59 peptides) matching the performance reported for large overlapping peptide pools (> 500 peptides). Furthermore, almost 70 % of the candidates (23 peptides) selected for a frequent HLA background (DRB1<em>03:01/</em>07:01) feature immunodominant responses ex vivo, validating our platform for accessing T cell epitopes at the population level. The analysis of the impact of processing constraints reveals distinct impact of proteolysis and solvent accessible surface area on epitope selection depending on the antigen. Thus, considering these properties for antigens in question should improve available epitope prediction tools.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.10.574975v1" target="_blank">Effective assessment of CD4+ T cell Immunodominance patterns: impact of antigen processing and HLA restriction</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) Co., Ltd. <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Massively parallel profiling of RNA-targeting CRISPR-Cas13d</strong> - CRISPR-Cas13d cleaves RNA and is used in vivo and for diagnostics. However, a systematic understanding of its RNA binding and cleavage specificity is lacking. Here, we describe an RNA Chip-Hybridized Association-Mapping Platform (RNA-CHAMP) for measuring the binding affinity for > 10,000 RNAs containing structural perturbations and other alterations relative to the CRISPR RNA (crRNA). Deep profiling of Cas13d reveals that it does not require a protospacer flanking sequence but is exquisitely…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human conjunctiva organoids to study ocular surface homeostasis and disease</strong> - The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inactivation mechanism of cold plasma combined with 222 nm ultraviolet for spike protein and its application in disinfecting of SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that has precipitated a worldwide pandemic of coronavirus disease since 2019. Developing an effective disinfection strategy is crucial to prevent the risk of surface cross-contamination by SARS-CoV-2. This study employed pseudovirus and the receptor-binding domain (RBD) protein of SARS-CoV-2 as models to investigate the spike protein inactivation process and its underlying mechanisms using a novel…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of TNF<em>-α</em> in the Pathogenesis of Migraine</strong> - CONCLUSION: To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences</strong> - After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2</strong> - Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2-h Receptor Binding and their Biological Evaluation In vitro</strong> - CONCLUSION: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lipid Metabolism Modulation during SARS-CoV-2 Infection: A Spotlight on Extracellular Vesicles and Therapeutic Prospects</strong> - Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>FHL2</em> Inhibits SARS-CoV-2 Replication by Enhancing <em>IFN-β</em> Expression through Regulating <em>IRF-3</em></strong> - SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with IFN-β exhibiting a notable inhibitory impact on SARS-CoV-2 replication. FHL2, acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and FHL2 remains unclear. In…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative Analysis of Cyclization Techniques in Stapled Peptides: Structural Insights into Protein-Protein Interactions in a SARS-CoV-2 Spike RBD/hACE2 Model System</strong> - Medicinal chemistry is constantly searching for new approaches to develop more effective and targeted therapeutic molecules. The design of peptidomimetics is a promising emerging strategy that is aimed at developing peptides that mimic or modulate the biological activity of proteins. Among these, stapled peptides stand out for their unique ability to stabilize highly frequent helical motifs, but they have failed to be systematically reported. Here, we exploit chemically diverse helix-inducing i,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs</strong> - Human society is facing the threat of various viruses. Proteases are promising targets for the treatment of viral infections. In this study, we collected and profiled 170 protease sequences from 125 viruses that infect humans. Approximately 73 of them are viral 3-chymotrypsin-like proteases (3CL^(pro)), and 11 are pepsin-like aspartic proteases (PAPs). Their sequences, structures, and substrate characteristics were carefully analyzed to identify their conserved nature for proposing a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Viral Targeting of Importin Alpha-Mediated Nuclear Import to Block Innate Immunity</strong> - Cellular nucleocytoplasmic trafficking is mediated by the importin family of nuclear transport proteins. The well-characterized importin alpha (IMPA) and importin beta (IMPB) nuclear import pathway plays a crucial role in the innate immune response to viral infection by mediating the nuclear import of transcription factors such as IRF3, NFκB, and STAT1. The nuclear transport of these transcription factors ultimately leads to the upregulation of a wide range of antiviral genes, including IFN and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>5’-cap RNA/SAM mimetic conjugates as bisubstrate inhibitors of viral RNA cap 2’-O-methyltransferases</strong> - Viral RNA cap 2’-O-methyltransferases are considered promising therapeutic targets for antiviral treatments, as they play a key role in the formation of viral RNA cap-1 structures to escape the host immune system. A better understanding of how they interact with their natural substrates (RNA and the methyl donor SAM) would enable the rational development of potent inhibitors. However, as few structures of 2’-O-MTases in complex with RNA have been described, little is known about substrate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Correction to: Dihydroisocoumarins of Hydrangea macrophylla var. thunbergii inhibit binding of the SARS-CoV-2 spike protein to ACE2</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Gut microbiota-derived butyrate promotes coronavirus TGEV infection through impairing RIG-I-triggered local type I interferon responses via class I HDAC inhibition</strong> - Swine enteric coronaviruses (SECoVs) infection in vivo alters the composition of short-chain fatty acids (SCFAs)-producing gut microbiota, but whether microbiota-derived SCFAs impact coronavirus gastrointestinal infection is largely unknown. Here, we demonstrated that SCFAs, particularly butyrate, substantially increased alphacoronavirus TGEV infection at the late stage of infection, without affecting viral attachment or internalization. Furthermore, enhancement of TGEV by butyrate depended on…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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