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171 lines
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<title>25 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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<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>CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment</strong> -
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<div>
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SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract and a vast proportion secrete the cytotoxic molecule Granzyme B. Using antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during 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/10.1101/2024.01.23.576505v1" target="_blank">CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment</a>
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</div></li>
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<li><strong>Adaptive advantage of deletion repair in the N terminal domain of the SARS-CoV-2 spike protein in variants of concern</strong> -
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<div>
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Mutations within the N-terminal domain (NTD) of the spike (S) protein play a pivotal role in the emergence of successful SARS-CoV-2 viral lineages. This study investigates the influence of novel combinations of NTD lineage-defining mutations found in the Alpha, Delta, and Omicron variants on viral success. We performed comparative genomics of more than 10 million public SARS-CoV-2 samples to decipher the transmission success of different NTD markers. Additionally, we characterized the viral phenotype of such markers in a surrogate in vitro system. We found that viruses bearing repaired deletions SDeltaH69/V70 and SDeltaY144 in Alpha background were associated with increased transmission rates. After the emergence of the Omicron BA.1 lineage, Alpha viruses harbouring both repaired deletions still showed increased transmission compared to their BA.1 counterparts. Remarkably, Alpha viruses with the SDeltaH69/V70 repair displayed the highest emergence rate, while those in BA.1 exhibited the lowest. Moreover, repaired deletions were more frequently observed among older individuals infected with Alpha, but not with BA.1. In vitro biological characterization of Omicron BA.1 spike deletion repair patterns revealed substantial differences with Alpha. In BA.1, SDeltaV143/Y145 repair enhanced fusogenicity and susceptibility to neutralization by vaccinated individuals' sera. In contrast, the SDeltaH69/V70 repair did not significantly alter these traits but reduced viral infectivity. Simultaneous repair of both deletions led to lower fusogenicity. These findings highlight the intricate genotype-phenotype landscape of the spike NTD in SARS-CoV-2, which impacts viral biology, transmission efficiency, and susceptibility to neutralization. Overall, this study advances our comprehension of SARS-CoV-2 evolution, carrying implications for public health and future research.
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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/10.1101/2024.01.23.575696v1" target="_blank">Adaptive advantage of deletion repair in the N terminal domain of the SARS-CoV-2 spike protein in variants of concern</a>
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</div></li>
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<li><strong>In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries</strong> -
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<div>
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The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
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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/sevkf/" target="_blank">In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries</a>
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</div></li>
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<li><strong>A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</strong> -
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<div>
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Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health 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/psyarxiv/n3dyf/" target="_blank">A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</a>
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<li><strong>A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</strong> -
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The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
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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/m4gpq/" target="_blank">A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</a>
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<li><strong>Correlates of Health-Protective Behavior During the Initial Days of the COVID-19 Outbreak in Norway</strong> -
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<div>
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The coronavirus outbreak manifested in Norway in March 2020. It was met with a combination of mandatory changes (closing of public institutions) and recommended changes (hygiene behavior, physical distancing). It has been emphasized that health-protective behavior such as increased hygiene or physical distancing are able to slow the spread of infections and flatten the curve. Drawing on previous health-psychological studies during the outbreak of various pandemics, we investigated psychological and demographic factors predicting the adoption and engagement in health-protective behavior and changes in such behavior, attitudes, and emotions over time. We recruited a non-representative sample of Norwegians (n = 8676) during a 15-day period (March 12–26 2020) at the beginning of the COVID-19 outbreak in Norway. Employing both traditional methods and exploratory machine learning, we replicated earlier findings that engagement in health-protective behavior is associated with specific demographic characteristics. Further, we observed that increased media exposure, perceiving measures as effective, and perceiving the outbreak as serious positively was related to engagement in health-protective behavior. We also found indications that hygiene and physical distancing behaviors were related to somewhat different psychological and demographic factors. Over the sampling period, reported engagement in physical distancing increased, while experienced concern or fear declined. Contrary to previous studies, we found no or only small positive predictions by confidence in authorities, knowledge about the outbreak, and perceived individual risk, while all of those variables were rather high. These findings provide guidance for health communications or interventions targeting the adoption of health-protective behaviors in order to diminish the spread of COVID-19.
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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/6vgf4/" target="_blank">Correlates of Health-Protective Behavior During the Initial Days of the COVID-19 Outbreak in Norway</a>
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</div></li>
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<li><strong>Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay</strong> -
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<div>
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New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including JN.1. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three doses of an ancestral vaccine but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). In our recent studies, however, the JN.1 VOI was found to be significantly more resistant to neutralisation by antibodies from those who had received the ancestral/BA.1 bivalent boost. Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The recent contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.
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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/10.1101/2023.10.21.563398v2" target="_blank">Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay</a>
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<li><strong>Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4" target="_blank">Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States</a>
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<li><strong>Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs</strong> -
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<div>
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COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.23.563669v5" target="_blank">Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs</a>
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<li><strong>SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis</strong> -
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Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.21.576509v1" target="_blank">SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis</a>
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<li><strong>Policy makers believe money motivates more than it does</strong> -
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To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccination—by 15.3 percentage points on average—the same financial incentive yielded a precisely estimated null effect on vaccination. We discuss when financial incentives are most likely to fail, and conclude that it is critical to educate policy makers on the potential pitfalls of employing financial incentives to promote contributions to public goods.
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🖺 Full Text HTML: <a href="https://osf.io/jq28n/" target="_blank">Policy makers believe money motivates more than it does</a>
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<li><strong>Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination</strong> -
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We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (KD < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC50 ~0.1-1.75 nM) and provided robust protection in vivo. Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.22.576742v1" target="_blank">Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination</a>
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<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
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SARS-CoV-2 employs its spike protein’s receptor binding domain (RBD) to enter host cells. The RBD is constantly subjected to immune responses, while requiring efficient binding to host cell receptors for successful infection. However, our understanding of how RBD’s biophysical properties contribute to SARS-CoV-2’s epidemiological fitness remains largely incomplete. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the discovery of a fitness function based on binding thermodynamics, we unravel the relationship between the biophysical properties of RBD variants and their contribution to viral fitness. We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by binding constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto a epistatic fitness landscape. We validate our findings through experimentally measured and machine learning (ML) estimated binding affinities, coupled with infectivity data derived from population-level sequencing. Our analysis reveals that this model effectively predicts the fitness of novel RBD variants and can account for the epistatic interactions among mutations, including explaining the later reversal of Q493R. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549087v3" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
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<li><strong>Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</strong> -
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X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory CT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.21.576083v1" target="_blank">Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</a>
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<li><strong>Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak.</strong> -
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OBJECTIVE At the beginning of 2020, hydroxychloroquine showed promising in vitro activity for Covid-19 and several studies were oriented to assess its safety and efficacy. However, after a few months, hydroxychloroquine has proved ineffective. The randomized controlled trials (RCTs) developed quickly and in different settings represent the scientific community capacity to assess drug repositioning effectiveness during a sanitary crisis. Therefore, a critical evaluation of the evidence generated can guide future efforts in analogous situations. We aimed to analyze the RCTs assessing the efficacy of hydroxychloroquine in treating Covid-19, describe their internal validity and power, and evaluate their contribution to the precision of the combined evidence for assessing the mortality outcome. STUDY DESIGN AND SETTINGS This meta-research included RCTs assessing hydroxychloroquine to treat patients diagnosed with Covid-19. It was part of an umbrella systematic review of methods/meta-research (PROSPERO: CRD42022360331) that included a comprehensive search in MEDLINE, EMBASE, Cochrane Library, and the Latin America Database - Lilacs. We retrieved studies published until January 10th, 2022. The risk of bias was assessed using Cochrane Risk of Bias (RoB) 2.0. We analyzed methodology of the studies, precision and random error change through time from pooled evidence, study comparators, patient important outcome, power in different magnitude of effects proxy. RESULTS A total of 22 RCT were included, from that 17 (77%) assessed hospitalized patients and five (23%) outpatients setting. Mortality was related as primary endpoint in only four studies, however half of the studies included composite endpoints including mortality as a component. The internal validity analysis using RoB2 found that eight studies (36%) had a high risk of bias. Only one study had sufficient power to evaluate a moderate magnitude of effect (RR = 0,7 on mortality). The standard error to evaluate efficacy on mortality did not change appreciably after October 2020. From Oct 2020 to Dec 2021, 18 additional studies were published with 2,429 patients recruited. CONCLUSION This meta-research highlights the impact that collaborative, and network scientific research have on informing clinical decision-making. Duplicate efforts create research waste as precision analysis shows that after October 2020, there was not appreciably changes in the precision of the pooled RCT evidence to estimate the hydroxychloroquine effect on mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.21.24301572v1" target="_blank">Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak.</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>Beneficial Effects of Natural Products on Management of Xerostomia</strong> - <b>Conditions</b>: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition <br/><b>Interventions</b>: Other: (Manuka honey-green tea- ginger) <br/><b>Sponsors</b>: British University In Egypt <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>Eficacia Ventilatoria y Remolacha</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Muscle Disorder; Fatigue <br/><b>Interventions</b>: Dietary Supplement: Remolacha <br/><b>Sponsors</b>: Hospital de Mataró <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>Diet and Fasting for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Long COVID <br/><b>Interventions</b>: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting <br/><b>Sponsors</b>: Pacific Northwest University of Health Sciences <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>The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia</strong> - <b>Conditions</b>: Post COVID-19 Condition <br/><b>Interventions</b>: Other: Protein powder and Resistance exercise <br/><b>Sponsors</b>: Mahidol University; National Health Security Office, Thailand <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>Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico</strong> - <b>Conditions</b>: Long Covid19 <br/><b>Interventions</b>: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) <br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH) <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>Treatment of Persistent Post-Covid-19 Smell and Taste Disorders</strong> - <b>Conditions</b>: Post-covid-19 Persistent Smell and Taste Disorders <br/><b>Interventions</b>: Drug: Cerebrolysin; Other: olfactory and gustatory trainings <br/><b>Sponsors</b>: Sherifa Ahmed Hamed <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>A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>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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<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>Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19</strong> - Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19. Methods: This was a pilot randomized, double-blind, placebo-controlled trial….</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>Biosurfactant potential and antiviral activity of multistrain probiotics</strong> - The COVID-19 caused by the SARS-CoV-2 has become a great threat to humans. However, there is no recommendation for an effective and safe drug to treat the disease. The strategy developed in this study is to utilize biosurfactant potential activity of Lactobacillus spp. and Rhodopseudomonas palustris probiotics to prevent the virus from entering human body. The outer membrane of the virus is comprising of phospholipid compounds. Biosurfactants, are known to have detergent-like properties (able to…</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>Online Group Supervision as Pedagogy: A Qualitative Inquiry of Student Mental Health Nurses’ Discourses and Participation</strong> - This study explored online group clinical supervision participation, as a component of pre-registration education following mental health nursing students’ clinical placements. Clinical supervision has historically been valued as a supportive strategy by healthcare professionals to develop practice and competence and prevent burnout. As many student nurses do not have access to clinical supervision via practice areas as a standardised process, their experiences of engaging in or benefitting from…</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>CRL4B E3 ligase recruited by PRPF19 inhibits SARS-CoV-2 infection by targeting ORF6 for ubiquitin-dependent degradation</strong> - The accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the…</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>Identification of amentoflavone as a potent SARS-CoV-2 M<sup>pro</sup> inhibitor: a combination of computational studies and in vitro biological evaluation</strong> - Small-molecule inhibitors of SARS-CoV-2 M^(pro) that block the active site pocket of the viral main protease have been considered potential therapeutics for the development of drugs against SARS-CoV-2. Here, we report the identification of amentoflavone (a biflavonoid) through docking-based virtual screening of a library comprised of 231 compounds consisting of flavonoids and isoflavonoids. The docking results were further substantiated through extensive analysis of the data obtained from…</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>Molecular dynamics simulation study on the binding mechanism between carbon nanotubes and RNA-dependent RNA polymerase</strong> - Carbon nanotubes (CNTs) have potential prospects in disease treatment, so it is of great significance to study CNTs as the possible inhibitors of RNA-dependent RNA polymerase (RdRp). Through the way of using the RdRp of SARS-COV-2 as a model, five armchair single-walled carbon nanotubes (SWCNTs) (namely Dn, which stands for CNTs (n, m = n), n = 3-7) and RdRp have been selected to study the interactions by means of molecular docking and molecular dynamics simulation. After five SWCNT-RdRp complex…</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 novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity</strong> - CONCLUSION: Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.</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 basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models</strong> - Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2…</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>Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19</strong> - CONCLUSIONS: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.</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>Impact of leisure satisfaction on perceived risk of infectious disease during the COVID-19 pandemic: evidence from new worker classes</strong> - CONCLUSION: This study verified the risk factors that inhibit leisure satisfaction among new worker classes that emerged during the COVID-19 pandemic. Furthermore, the psychological health of people suffering pandemic-related financial constraints was affected, as they experienced a lower quality of life owing to reduced leisure activities and satisfaction.</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>Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model</strong> - INTRODUCTION: Because prior immune checkpoint inhibitor (ICI) therapy in cancer patients presenting with COVID-19 may affect outcomes, we investigated the beta-coronavirus, murine hepatitis virus (MHV)-1, in a lethal pneumonia model in the absence (Study 1) or presence of prior programmed cell death ligand-1 (PD-L1) antibody (PD-L1mAb) treatment (Study 2).</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>Generation of SARS-CoV-2 spike receptor binding domain mutants and functional screening for immune evaders using a novel lentivirus-based system</strong> - The emergence of rapid and continuous mutations of severe acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein that increased with the Omicron variant points out the necessity to anticipate such mutations for conceiving specific and adaptable therapies to avoid another pandemic. The crucial target for the antibody treatment and vaccine design is the receptor binding domain (RBD) of the SARS-CoV-2 spike. It is also the site where the virus has shown its high ability to mutate 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>The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability</strong> - Paxlovid^(®), a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we…</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>Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK</strong> - The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling…</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 Analysis of Serodiagnostic Tests to Characterize the Incline and Decline of the Individual Humoral Immune Response in COVID-19 Patients: Impact on Diagnostic Management</strong> - Serodiagnostic tests for antibody detection to estimate the immunoprotective status regarding SARS-CoV-2 support diagnostic management. This study aimed to investigate the performance of serological assays for COVID-19 and elaborate on test-specific characteristics. Sequential samples (n = 636) of four panels (acute COVID-19, convalescent COVID-19 (partly vaccinated post-infection), pre-pandemic, and cross-reactive) were tested for IgG by indirect immunofluorescence test (IIFT) and EUROIMMUN…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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