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175 lines
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<title>28 November, 2023</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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</strong> -
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<div>
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Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvir in vitro following repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutants in vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation confers a high level of in vivo resistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness.
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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/10.1101/2023.11.22.568013v1" target="_blank">Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</a>
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</div></li>
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<li><strong>Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</strong> -
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Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.
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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/10.1101/2023.11.25.568670v1" target="_blank">Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</a>
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</div></li>
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<li><strong>XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants</strong> -
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<div>
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COVID-19 vaccines have recently been updated with the spike protein of SARS-Co-V-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.
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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/10.1101/2023.11.26.568730v1" target="_blank">XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections</strong> -
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<div>
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The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, and its subsequent variants has underscored the importance of understanding the host-viral molecular interactions to devise effective therapeutic strategies. A significant aspect of these interactions is the role of alternative splicing in modulating host responses and viral replication mechanisms. Our study sought to delineate the patterns of alternative splicing of RNAs from immune cells across different SARS-CoV-2 variants and vaccination statuses, utilizing a robust dataset of 190 RNA-seq samples from our previous studies, encompassing an average of 212 million reads per sample. We identified a dynamic alteration in alternative splicing and genes related to RNA splicing were highly deactivated in COVID-19 patients and showed variant- and vaccination-specific expression profiles. Overall, Omicron-infected patients exhibited a gene expression profile akin to healthy controls, unlike the Alpha or Beta variants. However, significantly, we found identified a subset of infected individuals, most pronounced in vaccinated patients infected with Omicron variant, that exhibited a specific dynamic in their alternative splicing patterns that was not widely shared amongst the other groups. Our findings underscore the complex interplay between SARS-CoV-2 variants, vaccination-induced immune responses, and alternative splicing, emphasizing the necessity for further investigations into these molecular cross-talks to foster deeper understanding and guide strategic therapeutic development.
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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/10.1101/2023.11.24.568603v1" target="_blank">Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections</a>
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</div></li>
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<li><strong>Evolution-guided large language model is a predictor of virus mutation trends</strong> -
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<div>
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Emerging viral infections, especially the global pandemic COVID-19, have had catastrophic impacts on public health worldwide. The culprit of this pandemic, SARS-CoV-2, continues to evolve, giving rise to numerous sublineages with distinct characteristics. The traditional post-hoc wet-lab approach is lagging behind, and it cannot quickly predict the evolutionary trends of the virus while consuming high costs. Capturing the evolutionary drivers of virus and predicting potential high-risk mutations has become an urgent and critical problem to address. To tackle this challenge, we introduce ProtFound-V, an evolution-inspired deep-learning framework designed to explore the mutational trajectory of virus. Take SARS-CoV-2 as an example, ProtFound-V accurately identifies the evolutionary advantage of Omicron and proposes evolutionary trends consistent with wet-lab experiments through in silico deep mutational scanning. This showcases the potential of deep learning predictions to replace traditional wet-lab experimental measurements. With the evolution-guided large language model, ProtFound-V presents a new state-of-the-art performance in key property predictions. Despite the challenge posed by epistasis to model generalization, ProtFound-V remains robust when extrapolating to lineages with different genetic backgrounds. Overall, this work paves the way for rapid responses to emerging viral infections, allowing for a plug-and-play approach to understanding and predicting virus evolution.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.27.568815v1" target="_blank">Evolution-guided large language model is a predictor of virus mutation trends</a>
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</div></li>
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<li><strong>Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins</strong> -
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<div>
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The dysregulation of cellular signaling upon SARS-CoV-2 infection is mediated via direct protein interactions, with the human protein kinases constituting the major impact nodes in the signaling networks. Here, we employed a targeted yeast two-hybrid matrix approach to identify direct SARS-CoV-2 protein interactions with an extensive set of human kinases. We discovered 51 interactions involving 14 SARS-CoV-2 proteins and 29 human kinases, including many of the CAMK and CMGC kinase family members, as well as non-receptor tyrosine kinases. By integrating the interactions identified in our screen with transcriptomics and phospho-proteomics data, we revealed connections between SARS-CoV-2 protein interactions, kinase activity changes, and the cellular phospho-response to infection and identified altered activity patterns in infected cells for AURKB, CDK2, CDK4, CDK7, ABL2, PIM2, PLK1, NEK2, TRIB3, RIPK2, MAPK13, and MAPK14. Finally, we demonstrated direct inhibition of the FER human tyrosine kinase by the SARS-CoV-2 auxiliary protein ORF6, hinting at pressures underlying ORF6 changes observed in recent SARS-CoV-2 strains. Our study expands the SARS-CoV-2 - host interaction knowledge, illuminating the critical role of dysregulated kinase signaling during SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.27.568816v1" target="_blank">Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins</a>
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</div></li>
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<li><strong>Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.</strong> -
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<div>
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Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.
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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/10.1101/2023.11.24.568354v1" target="_blank">Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.</a>
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<li><strong>The antiviral potential of the antiandrogen enzalutamide and the viral-androgen interplay in seasonal coronaviruses</strong> -
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<div>
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The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly against prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and replication in both TMPRSS2- and non-expressing immortalised cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E- and OC43-infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72h post-infection. The virus-mediated effect to AR signaling was further confirmed with a consensus androgen response element (ARE)-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen signaling, offering insights for potential antiviral interventions.
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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/10.1101/2023.11.25.568685v1" target="_blank">The antiviral potential of the antiandrogen enzalutamide and the viral-androgen interplay in seasonal coronaviruses</a>
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<li><strong>Hybrid Course Dynamics in Physical Education: Insights from a Leading Chinese Public University</strong> -
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<div>
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Against the backdrop of technological advances, educational reforms, and the impact of the COVID-19 pandemic, hybrid courses have become increasingly popular in higher education in China. The study draws from existing theoretical knowledge and practical experiences to provide insights on the feasibility and potential benefits of using the hybrid course modality in physical education, aiming to investigate the applicability of the hybrid course modality in promoting undergraduate students’ engagement in physical education courses at a large public university in China. It also focuses on practical implications of the hybrid course modality to enhance physical education courses in Chinese higher education institutions, by exploring how this modality can serve as a useful tool in such courses.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/hcevw/" target="_blank">Hybrid Course Dynamics in Physical Education: Insights from a Leading Chinese Public University</a>
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<li><strong>The Situation During the COVID-19 Pandemic: A Snapshot in Germany</strong> -
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During government-implemented restrictions in the wake of the COVID-19 pandemic, people’s everyday lives changed profoundly. However, there is to date little research chronicling how people perceived their changed everyday lives and which consequences this had. In a two-wave study, we examined the psychological characteristics of people’s situations and their correlates during shutdown in a large German sample (NT1 = 1,353; NT2 = 446). First, we compared characteristics during government-issued restrictions with retrospective accounts from before and with a follow-up assessment 6 to 7 months later when many restrictions had been lifted. We found that mean levels were lower and variances were higher for most characteristics during the shutdown. Second, the experience of certain situation characteristics was associated in meaningful and theoretically expected ways with people’s traits, appraisals of the COVID-19 crisis, and subjective well-being. Lastly, situation characteristics often substantially explained the associations of traits with appraisals and well-being. Our findings highlight the importance of considering perceived situations as these contribute to people’s functioning during crises.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/49chx/" target="_blank">The Situation During the COVID-19 Pandemic: A Snapshot in Germany</a>
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<li><strong>Who is impacted? Personality predicts individual differences in psychological consequences of the COVID-19 pandemic in Germany</strong> -
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The COVID-19 pandemic has led to changes in people’s private and public lives that are unprecedented in modern history. However, little is known about the differential psychological consequences of restrictions that have been imposed to fight the pandemic. In a large and diverse German sample (N = 1,320), we examined how individual differences in psychological consequences of the pandemic (perceived restrictiveness of government-supported measures; global pandemic-related appraisals; subjective well-being) were associated with a broad set of faceted personality traits (Big Five, Honesty-Humility, Dark Triad). Facets of Extraversion, Neuroticism, and Openness were among the strongest and most important predictors of psychological outcomes, even after controlling for basic socio-demographic variables (gender, age). These findings suggest that psychological consequences of the pandemic depend on personality and thus add to the growing literature on the importance of considering individual differences in crisis situations.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/s65ux/" target="_blank">Who is impacted? Personality predicts individual differences in psychological consequences of the COVID-19 pandemic in Germany</a>
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<li><strong>A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</strong> -
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During the COVID-19 pandemic, many countries and regions investigated the potential use of wastewater-based disease surveillance as an early warning system. Initially, methods were created to detect the presence of SARS-CoV-2 RNA in wastewater. Investigators have since conducted extensive studies to examine the link between viral concentration in wastewater and COVID-19 cases in areas served by sewage treatment plants over time. However, only a few reports have attempted to create predictive models for hospitalizations at county-level based on SARS-CoV-2 RNA concentrations in wastewater. This study implemented a linear mixed-effects model that observes the association between levels of virus in wastewater and county-level hospitalizations. The model was then utilized to predict short-term county-level hospitalization trends in 21 counties in California based on data from March 21, 2022, to May 21, 2023. The modeling framework proposed here permits repeated measurements as well as fixed and random effects. The model that assumed wastewater data as an input variable, instead of cases or test positivity rate, showed strong performance and successfully captured trends in hospitalizations. Additionally, the model allows for the prediction of SARS-CoV-2 hospitalizations two weeks ahead. Forecasts of COVID-19 hospitalizations could provide crucial information for hospitals to better allocate resources and prepare for potential surges in patient numbers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.14.23293945v4" target="_blank">A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</a>
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<li><strong>Projecting COVID-19 intensive care admissions in the Netherlands for policy advice: February 2020 to January 2021</strong> -
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Introduction: Model projections of COVID-19 incidence into the future help policy makers about decisions to implement or lift control measures. During 2020, policy makers in the Netherlands were informed on a weekly basis with short-term projections of COVID-19 intensive care unit (ICU) admissions. Here we present the model and the procedure by which it was updated. Methods: the projections were produced using an age-structured transmission model. A consistent, incremental update procedure that integrated all new surveillance and hospital data was conducted weekly. First, up-to-date estimates for most parameter values were obtained through re-analysis of all data sources. Then, estimates were made for changes in the age-specific contact rates in response to policy changes. Finally, a piecewise constant transmission rate was estimated by fitting the model to reported daily ICU admissions, with a change point analysis guided by Akaike9s Information Criterion. Results: The model and update procedure allowed us to make mostly accurate weekly projections, accounting for recent and future policy changes, and to adapt the estimated effectiveness of the policy changes based only on the natural accumulation of incoming data. Discussion: The model incorporates basic epidemiological principles and most model parameters were estimated per data source. Therefore, it had potential to be adapted to a more complex epidemiological situation, as it would develop after 2020.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.30.23291989v3" target="_blank">Projecting COVID-19 intensive care admissions in the Netherlands for policy advice: February 2020 to January 2021</a>
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<li><strong>Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs</strong> -
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Micro-physiological systems (MPS) are set to play a vital role in preclinical studies, particularly in the context of future viral pandemics. Nonetheless, the development of MPS is often impeded by the scarcity of reliable cell sources, especially when seeking various organs or tissues from a single patient for comparative analysis of the host immune response. Herein, we developed human airway-on-chip and alveolus-on-chip models using induced pluripotent stem cell (iPSC)-derived isogenic lung progenitor cells. Both models demonstrated the replication of two different respiratory viruses, namely SARS-CoV-2 and Influenza, as well as related cellular damage and innate immune responses-on-chip. Our findings reveal distinct immune responses to SARS-CoV-2 in the proximal and distal lung-on-chip models. The airway chips exhibited a robust interferon (IFN)-dependent immune response, whereas the alveolus chips exhibited dysregulated IFN activation but a significantly upregulated chemokine pathway. In contrast, Influenza virus infection induced a more pronounced immune response and cellular damage in both chip models compared to SARS-CoV-2. Thus, iPSC-derived lung-on-chip models may aid in quickly gaining insights into viral pathology and screening potential drugs for future pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.24.568532v1" target="_blank">Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs</a>
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<li><strong>REPORT : Study on ‘Institutionalizing Science Advice to Governments</strong> -
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The provision of appropriate science advice to governments is of national, regional, and global importance. However, many countries, especially in the developing world, lack effective framework to provide science advice to governments, which was laid bare during the COVID-19 pandemic. Hence, there is an urgent need to describe and analyse the structures and processes providing science advice to governments with a view to strengthening science advice. Science advice requires synthesizing and brokering valid, relevant, and reliable scientific evidence in respect of different policies. The National Academy of Sciences of Sri Lanka conducted a study on the status and processes of institutionalizing Science Advice to Governments in the Australasian region. The aims of the study were to a) propose and facilitate the development and strengthening of systematic science advice in member countries and its institutionalization b) Improve awareness among partners on a range of laws and regulations that exist legitimizing institutions and the processes used for government science advice c) develop capacities of participating academies in providing science advice d) enable academies to play a role and be part of the science advice process The methodology included administration of a structured questionnaire to gather data for the Situation Analysis with respect to science advice in partner countries. The questionnaire responses were categorized under several headings identified as the ‘Colombo Framework’: Selection of advisors, organizational structures to provide advice, the process followed to collate and synthesize advice, the process of communication, and evaluation of the process and impact of advice. The results showed a diversity of responses indicating a range of structures and processes: • The structures and types of advisors included, chief science advisor or advisors, a science advisory office or agency, science advisory boards, science advisory councils and ad-hoc arrangements during emergencies or crises, such as task forces. • Selection of advisors varied from appointments by an executive authority to nominations by science organizations or selection processes based on academic credentials. • The initial framing of questions requiring science advice were by policymakers, parliament committee or the President and advisory council. • Collation and synthesizing evidence: The methods used included systematic reviews, meta-analyses, through surveys, consultative meetings, expert opinion, foresight tools and workshops and/meetings of the experts where the evidence was reviewed. • The process of communicating science advice included reports issued by the science advisors, or advice directed to the Presidential Office, to Cabinet office, or submitted through Secretary of the Ministry of Science and Technology to the Head of State, or reports to the relevant minister and presidential secretariat. • The impact of science advice on policy was rarely evaluated. • Case Studies for individual countries supplemented the situation analysis for that country. • A SWOT analyses was compiled based on each country responses to reflect the totality of responses and for guidance in drafting a framework for Roadmaps for each country. As part of the project a three-day workshop was held in Colombo, Sri Lanka on ‘Institutionalizing Science Advice to Governments’ 6-8 July 2023. A descriptive ‘Colombo Declaration’ was released calling on governments to partner with scientists and demonstrate stronger commitment in strengthening action to institutionalize science advice to governments. The concluding session described future actions of developing Roadmaps and Case Studies by each partner country. The contextualized roadmaps will be developed through an iterative process and ‘work in progress’ submitted by most partner agencies were included in the report. The key outcomes of the Project were the following: 1. Documentation of Science Advice Systems in countries with situation analysis, reinforced with case studies an
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/ygp84/" target="_blank">REPORT : Study on ‘Institutionalizing Science Advice to Governments</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>A Randomized Trial Evaluating a mRNA VLP Vaccine’s Immunogenicity and Safety for COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: AZD9838; Biological: Licensed mRNA vaccine <br/><b>Sponsors</b>: AstraZeneca <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>Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Metformin; Other: Placebo <br/><b>Sponsors</b>: Trust for Vaccines and Immunization, Pakistan <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>“The Effect of Aerobic Exercise and Strength Training on Physical Activity Level, Quality of Life and Anxiety-Stress Disorder in Young Adults With and Without Covid-19”</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Aerobic Exercise and Strength Training <br/><b>Sponsors</b>: Pamukkale 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>Vale+Tú Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Group Problem Solving; Behavioral: Standard of Care; Behavioral: Booster session <br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Institute on Minority Health and Health Disparities (NIMHD) <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>Safety Study of SLV213 for the Treatment of COVID-19.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Placebo for SLV213; Drug: SLV213 <br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID) <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>Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Diagnostic Test: RIPH2 <br/><b>Sponsors</b>: CerbaXpert <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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19 <br/><b>Interventions</b>: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources <br/><b>Sponsors</b>: Idaho State University <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>Promoting Engagement and COVID-19 Testing for Health</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging <br/><b>Sponsors</b>: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology <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>Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19</strong> - <b>Conditions</b>: Certain Disorders Involving the Immune Mechanism <br/><b>Interventions</b>: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 <br/><b>Sponsors</b>: University Hospital, Tours <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>Water-based Activity to Enhance Recovery in Long COVID</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Behavioral: WATER+CT; Behavioral: Usual Care <br/><b>Sponsors</b>: VA Office of Research and Development <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>Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID</strong> - <b>Conditions</b>: Persistent COVID-19 <br/><b>Interventions</b>: Other: exercise programe <br/><b>Sponsors</b>: Facultat de ciencies de la Salut Universitat Ramon Llull <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>Performance Evaluation of the Lucira COVID-19 & Flu Test</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Device: Lucira COVID-19 & Flu Test <br/><b>Sponsors</b>: Lucira Health Inc <br/><b>Completed</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>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <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>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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>SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling</strong> - Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since emerging in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV…</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>Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes</strong> - Critically ill people 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. In 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…</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>C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?</strong> - From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement…</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>The association between BIS/BAS and fear of COVID-19 infection among women</strong> - CONCLUSIONS: The BIS weakly, but significantly correlated with women’s fear of their loved ones being infected by COVID-19. This study highlights the possible role of the BIS mechanism in women’s response to COVID-19-related fear, but only when the threat affects loved ones. Comparative studies between men and women are necessary.</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>Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome</strong> - Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS 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>Achievement Emotions of Medical Students: Do They Predict Self-regulated Learning and Burnout in an Online Learning Environment?</strong> - BACKGROUND: Achievement emotions have been proven as important indicators of students’ academic performance in traditional classrooms and beyond. In the online learning contexts, previous studies have indicated that achievement emotions would affect students’ adoption of self-regulated learning strategies and further predict their learning outcomes. However, the pathway regarding how different positive and negative achievement emotions might affect students’ burnout through self-regulated…</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>Linoleic acid: a natural feed compound against porcine epidemic diarrhea disease</strong> - Porcine epidemic diarrhea virus (PEDV) is a pig coronavirus that causes severe diarrhea and high mortality in piglets, but as no effective drugs are available, this virus threatens the pig industry. Here, we found that the intestinal contents of specific pathogen-free pigs effectively blocked PEDV invasion. Through proteomic and metabolic analyses of the intestinal contents, we screened 10 metabolites to investigate their function and found that linoleic acid (LA) significantly inhibited PEDV…</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>Platelet factor 4(PF4) and its multiple roles in diseases</strong> - Platelet factor 4 (PF4) combines with heparin to form an antigen that could produce IgG antibodies and participate in heparin-induced thrombocytopenia (HIT). PF4 has attracted wide attention due to its role in novel coronavirus vaccine-19 (COVID-9)-induced immune thrombotic thrombocytopenia (VITT) and cognitive impairments. The electrostatic interaction between PF4 and negatively charged molecules is vital in the progression of VITT, which is similar to HIT. Emerging evidence suggests its…</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>Design of MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies</strong> - Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix. This was achieved by the use of…</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>A phenothiazine urea derivative broadly inhibits coronavirus replication via viral protease inhibition</strong> - Coronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (M^(pro)) and papain-like protease (PL^(pro)), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 M^(pro) and PL^(pro) protease activity…</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>Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains</strong> - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread as a pandemic and caused damage to people’s lives and countries’ economies. The spike (S) protein of SARS-CoV-2 contains a cleavage motif, Arg-X-X-Arg, for furin and furin-like enzymes at the boundary of the S1/S2 subunits. Given that cleavage plays a crucial role in S protein activation and viral entry, the cleavage motif was selected as the target. Our previous fluorogenic…</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>Efficient SARS-CoV-2 infection antagonization by rhACE2 ectodomain multimerized onto the Avidin-Nucleic-Acid-NanoASsembly</strong> - Nanodecoy systems based on analogues of viral cellular receptors assembled onto fluid lipid-based membranes of nano/extravescicles are potential new tools to complement classic therapeutic or preventive antiviral approaches. The need for lipid-based membranes for transmembrane receptor anchorage may pose technical challenges along industrial translation, calling for alternative geometries for receptor multimerization. Here we developed a semisynthetic self-assembling SARS-CoV-2 nanodecoy by…</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>Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds</strong> - CONCLUSION: The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients.</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>Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens</strong> - The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin-phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag….</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 Immune Response after Vaccination with SOBERANA<sup>®</sup> 02 and SOBERANA<sup>®</sup> plus Heterologous Scheme and Natural Infection in Young Children</strong> - (1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5-11 years) vaccinated with the RBD-based vaccines SOBERANA^(®) 02 and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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