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186 lines
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<title>26 January, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Framing COVID-19 preprint research as uncertain: A mixed-method study of public reactions</strong> -
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<div>
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During the COVID-19 pandemic, journalists were encouraged to convey uncertainty surrounding preliminary scientific evidence, including mentioning when research is unpublished or unverified by peer review. To understand how public audiences interpret this information, we conducted a mixed method study with U.S. adults. Participants read a news article about preprint COVID-19 vaccine research in early April 2021, just as the vaccine was becoming widely available to the U.S. public. We modified the article to test two ways of conveying uncertainty (hedging of scientific claims and mention of preprint status) in a 2 × 2 between-participants factorial design. To complement this, we collected open-ended data to assess participants’ understanding of the concept of a scientific preprint. In all, participants who read hedged (vs. unhedged) versions of the article reported less favorable vaccine attitudes and intentions and found the scientists and news reporting less trustworthy. These effects were moderated by participants’ epistemic beliefs and their preference for information about scientific uncertainty. However, there was no impact of describing the study as a preprint, and participants’ qualitative responses indicated a limited understanding of the concept. We discuss implications of these findings for communicating initial scientific evidence to the public and we outline important next steps for research and theory-building.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/wcd58/" target="_blank">Framing COVID-19 preprint research as uncertain: A mixed-method study of public reactions</a>
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</div></li>
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<li><strong>In the name of health and illness: An inquiry into Covid-19 vaccination policy in postsecondary education in Canada</strong> -
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<div>
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Since the launch of the Covid-19 global vaccination campaign in December of 2020, vaccination in postsecondary institutions has been a contested issue. International evidence indicates that these institutions have achieved high vaccination rates and Canadian public health agencies exclude them entirely from the list of institutions at risk of outbreaks. On the other hand, influential observers, and postsecondary institutions themselves insist that not only achieving, but also maintaining, “up-to-date” vaccination - through mandates if necessary – remains critical to contain the crisis. However, with the increasing recognition that vaccines do not stop viral spread, that young populations are at exceedingly low risk of severe Covid-19, hospitalization, and death - with a survival rate of over 99.98% - and that mandated medical interventions have a troubled history with repercussions to this day, the soundness of current vaccination policies in postsecondary institutions cannot be assumed. Drawing from the medicalization tradition and interpretive phenomenology, our study explores, through in-depth interviews, how vaccination policies within and beyond postsecondary institutions have shaped perceptions of the Covid-19 crisis, beliefs about the role, risks, and benefits of vaccination, and life choices and chances of students in Canada. We find that students largely comply with vaccination policies, whether by conviction, convenience, or coercion, and that the discourse and social practices promoted by the policies limit opportunities for free debate and exchange across vaccination statuses. Regardless of this status, students do resist, albeit very limitedly given the high cost of noncompliance. We discuss the implications of our findings for policy, equity, and for the power of medical social control in the Covid-19 era.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/gdbj3/" target="_blank">In the name of health and illness: An inquiry into Covid-19 vaccination policy in postsecondary education in Canada</a>
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</div></li>
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<li><strong>The Evolution of Local Energetic Frustration in Protein Families</strong> -
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<div>
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Energetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We have analyzed these signals in very well studied cases such as PDZ, SH3, alpha and beta globins and RAS families. Recent advances in protein structure prediction make it possible to analyze a vast majority of the protein space. An automatic and unsupervised proteome-wide analysis on the SARS-CoV-2 virus demonstrates the potential of our approach to enhance our understanding of the natural phenotypic diversity of protein families beyond single protein instances. We have applied our method to modify biophysical properties of natural proteins based on their family properties, as well as perform unsupervised analysis of large datasets to shed light on the physicochemical signatures of poorly characterized proteins such as emergent pathogens.
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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/10.1101/2023.01.25.525527v1" target="_blank">The Evolution of Local Energetic Frustration in Protein Families</a>
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</div></li>
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<li><strong>Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus</strong> -
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<div>
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During the spread of the COVID-19 pandemic, the SARS-CoV-2 coronavirus underwent mutation and recombination events that altered its genome compositional structure, thus providing an unprecedented opportunity to search for adaptive evolutionary trends in real-time. The mutation rate in coronavirus is known to be lower than expected for neutral evolution, thus suggesting a role for natural selection. We summarize the compositional heterogeneity of each viral genome by computing its Sequence Compositional Complexity (SCC). To study the full range of SCC diversity, random samples of high quality coronavirus genomes covering pandemic time span were analyzed. We then search for evolutionary trends that could inform on the adaptive process of the virus to its human host by computing the phylogenetic ridge regression of SCC against time (i.e., the collection date of each viral isolate). In early samples, we find no statistical support for any trend in SCC, although the viral genome appears to evolve faster than Brownian Motion (BM) expectation. However, in samples taken after the emergence of high fitness variants, and despite the brief time span elapsed, a driven decreasing trend for SCC, and an increasing one for its absolute evolutionary rate, are detected, pointing to a role for selection in the evolution of SCC in coronavirus genomes. We conclude that the higher fitness of variant genomes leads to adaptive trends of SCC over pandemic time in the coronavirus.
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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/10.1101/2021.11.06.467547v6" target="_blank">Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus</a>
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</div></li>
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<li><strong>Grandparents and Parental Labor Supply during COVID-19 Pandemic</strong> -
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<div>
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This study examines whether and to what extent the availability of grandparents in the home plays a buffering role in the labor supply of parents of children aged 0-5 during the COVID-19 pandemic. The role of grandparents as a childcare resource and its association with parents’ labor supply have received increasing attention in the literature. Limited childcare options during the pandemic underscore the need to investigate how working parents manage the double burden of family and work and what role grandparents could play. I use monthly data from the Current Population Survey (CPS) from January to May 2019 and 2020. Using a propensity score matching method, 6,599 parents in three-generational households were matched to 82,704 parents in two-generational households. Then, I employ a difference-in-difference approach with propensity score matched samples, taking advantage of two sources of variation: an exogenous shock from the pandemic and the availability of grandparents in the home. Parents living with grandparents are 2.90 percentage points more likely to have worked last week and worked 1.36 hours longer during the pandemic relative to parents in a two-generational household. The effects of the availability of coresident grandparents are more pronounced among single and low-educated parents than their counterparts. Results highlight that grandparents played a buffering role in mitigating the adverse impact of the pandemic on parental labor supply. This study sheds light on the importance of grandparental care specifically and informal care and home-based care in general. It also provides policy implications for strengthening the childcare system.
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</div>
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🖺 Full Text HTML: <a href="https://osf.io/jxyvn/" target="_blank">Grandparents and Parental Labor Supply during COVID-19 Pandemic</a>
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</div></li>
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<li><strong>The impact of COVID-19 lockdown on a cohort of adults with recurrent major depressive disorder from Catalonia: a decentralized longitudinal study using remote measurement technology</strong> -
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The present study analyzes the effects on depression levels of each containment phase of the first wave of COVID-19 in a cohort of adults with a history of major depressive disorder (MDD). This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8) and anxiety with the Generalized Anxiety Disorder-7 (GAD-7). A total of 121 participants from Catalonia were registered from November 1, 2019, to October 16, 2020. Levels of depression were explored across the phases (pre-lockdown, lockdown, four post-lockdown phases) of the restrictions imposed by the Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in the depressive severity was found during the lockdown and phase 0 (early post-lockdown), as compared with pre-lockdown phase in this sample with a history of MDD. Those with low pre-lockdown depression experienced a higher increase in depression levels during the new-normality. We observed a significant decrease in the depression levels during the new-normality in those with high pre-lockdown depression, compared to the pre-lockdown period. These findings suggest that COVID-19 restrictions impacted on the depression of individuals diagnosed with MDD, depending on their pre-lockdown depression levels.
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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/10.1101/2023.01.24.23284906v1" target="_blank">The impact of COVID-19 lockdown on a cohort of adults with recurrent major depressive disorder from Catalonia: a decentralized longitudinal study using remote measurement technology</a>
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</div></li>
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<li><strong>A role for Toll-like receptor 3 in lung vascular remodeling associated with SARS-CoV-2 infection</strong> -
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<div>
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Cardiovascular sequelae of severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) disease 2019 (COVID-19) contribute to the complications of the disease. One potential complication is lung vascular remodeling, but the exact cause is still unknown. We hypothesized that endothelial TLR3 insufficiency contributes to lung vascular remodeling induced by SARS-CoV-2. In the lungs of COVID-19 patients and SARS-CoV-2 infected Syrian hamsters, we discovered thickening of the pulmonary artery media and microvascular rarefaction, which were associated with decreased TLR3 expression in lung tissue and pulmonary artery endothelial cells (ECs). In vitro, SARS-CoV-2 infection reduced endothelial TLR3 expression. Following infection with mouse-adapted (MA) SARS-CoV-2, TLR3 knockout mice displayed heightened pulmonary artery remodeling and endothelial apoptosis. Treatment with the TLR3 agonist polyinosinic:polycytidylic acid reduced lung tissue damage, lung vascular remodeling, and endothelial apoptosis associated with MA SARS-CoV-2 infection. In conclusion, repression of endothelial TLR3 is a potential mechanism of SARS-CoV-2 infection associated lung vascular remodeling and enhancing TLR3 signaling is a potential strategy for treatment.
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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/10.1101/2023.01.25.524586v1" target="_blank">A role for Toll-like receptor 3 in lung vascular remodeling associated with SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination</strong> -
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<div>
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Respiratory mucosal immunity induced by vaccination is vital for protection from coronavirus infection in animal models. In humans, SARS-CoV-2 immunity has been studied extensively in blood. However, the capacity of peripheral vaccination to generate sustained humoral and cellular immunity in the lung mucosa, and how this is influenced by prior SARS-CoV-2 infection, is unknown. Bronchoalveolar lavage samples obtained from vaccinated donors with or without prior infection revealed enrichment of spike-specific antibodies, class-switched memory B cells and T cells in the lung mucosa compared to the periphery in the setting of hybrid immunity, whereas in the context of vaccination alone, local anti-viral immunity was limited to antibody responses. Spike-specific T cells persisted in the lung mucosa for up to 5 months post-vaccination and multi-specific T cell responses were detected at least up to 11 months post-infection. Thus, durable lung mucosal immunity against SARS-CoV-2 seen after hybrid exposure cannot be achieved by peripheral vaccination alone, supporting the need for vaccines targeting the airways.
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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/10.1101/2023.01.25.525485v1" target="_blank">Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination</a>
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<li><strong>RAMEN identifies effective indicators for severe COVID and Long COVID patients</strong> -
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<div>
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The outbreak of the COVID-19 pandemic caused catastrophic socioeconomic consequences and fundamentally reshaped the lives of billions across the globe. Our current understanding of the relationships between clinical variables (demographics, symptoms, follow-up symptoms, comorbidities, treatments, lab results, complications, and other clinical measurements) and COVID-19 outcomes remains obscure. Various computational approaches have been employed to elucidate the relationships between different COVID-19 clinical variables and their contributions to the disease outcomes. However, it is often challenging to capture the indirect relationships, as well as the direction of those relationships, with the conventional pairwise correlation methods. Graphical models (e.g., Bayesian networks) can address these limitations but are computationally expensive, which substantially limits their applications in reconstructing relationship networks ofumpteen clinical variables. In this study, we have developed a method named RAMEN, which employs Genetic Algorithm and random walks to infer the Bayesian relationship network between clinical variables. We applied RAMEN to a comprehensive COVID-19 dataset, Biobanque Quebecoise de la COVID-19 (BQC19). Most of the clinical variables in our reconstructed Bayesian network associated with COVID-19 severity, or long COVID, are supported by existing literature. We further computationally verified the effectiveness of the RAMEN method with statistical examinations of the multi-omics measurements (Clinical variables, RNA-seq, and Somascan) of the BQC19 data and simulations. The accurate inference of the relationships between clinical variables and disease outcomes powered by RAMEN will significantly advance the development of effective and early diagnostics of severe COVID-19 and long COVID, which can help save millions of lives.
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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/10.1101/2023.01.24.525413v1" target="_blank">RAMEN identifies effective indicators for severe COVID and Long COVID patients</a>
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<li><strong>Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers</strong> -
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We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284881v1" target="_blank">Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers</a>
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<li><strong>Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study</strong> -
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Objective To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community. Design Retrospective cohort study of non-hospitalised adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank. Setting A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK. Participants Adult patients with COVID-19 in the community, at higher risk of hospitalisation and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022. Interventions Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales. Main outcome measures All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2. Statistical analysis Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales. Results Between 16th December 2021 and 22nd April 2022, 7,103 higher-risk patients were eligible for inclusion in the study. Of these, 2,040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1,079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalisation or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalisation or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods. Conclusions In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalisation or death than those not receiving treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.24.23284916v1" target="_blank">Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study</a>
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<li><strong>Influenza transmission dynamics quantified from wastewater</strong> -
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Influenza infections are challenging to monitor at the population level due to a high proportion of mild and asymptomatic cases and confounding of symptoms with other common circulating respiratory diseases, including COVID-19. Alternate methods capable of tracking cases outside of clinical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviors. We quantified influenza A and B virus loads from influent at Switzerland9s three largest wastewater treatment plants, serving about 12% of the Swiss population. We estimated trends in infection incidence and the effective reproductive number Re in these catchments during a 2021/22 epidemic and compared our estimates to clinical influenza surveillance data. We showed that wastewater-based incidence is better aligned with catchment-level confirmed cases than national ILI, and that only the wastewater data capture a peak in incidence in December 2021. We further estimated Re to have been below 1.05 after introduction of work from home measures in December 2021 and above 0.97 after these measures were relaxed in two out of three catchments based on wastewater data. The third catchment yielded qualitatively the same results, although with wider confidence intervals. The confirmed-case data yielded comparatively less precise estimates that include 1 before and during the period of measures. On the basis of this research we developed an online dashboard for wastewater-based influenza surveillance in Switzerland where we will continue to monitor the onset and dynamics of the 2022/23 flu season.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.23.23284894v1" target="_blank">Influenza transmission dynamics quantified from wastewater</a>
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<li><strong>TONSILS ARE MAJOR SITES OF PROLONGED SARS-COV-2 INFECTION IN CHILDREN</strong> -
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In the present study, we show that SARS-CoV-2 can infect palatine tonsils and adenoids in children without symptoms of COVID-19, with no history of recent upper airway infection. We studied 48 children undergoing tonsillectomy due to snoring/OSA or recurrent tonsillitis between October 2020 and September 2021. Briefly, nasal cytobrush (NC), nasal wash (NW) and tonsillar tissue fragments obtained at surgery were tested by RT-PCR, immunohistochemistry (IHC), flow cytometry and neutralization assay. We detected the presence of SARS-CoV-2 in at least one specimen tested in 25% of patients (20% in palatine tonsils and 16.27% in adenoids, 10.41% of NC and 6.25% of NW). Importantly, in 2 of the children there was evidence of laboratory-confirmed acute infection 2 and 5 months before surgery. IHC revealed the presence of SARS-CoV-2 nucleoprotein in epithelial surface and in lymphoid cells in both extrafollicular and follicular regions, in adenoids and palatine tonsils. Flow cytometry showed that CD20+ B lymphocytes were the most infected phenotypes by SARS-CoV-2 NP, followed by CD4+ and CD8+ T lymphocytes, and CD14+ macrophages and dendritic cells. Additionally, IF indicated that SARS-CoV-2-infected tonsillar tissues had increased expression of ACE2 and TMPRSS2. NGS sequencing demonstrated the presence of different SARS CoV-2 variants in tonsils from different tissues. SARS-CoV-2 antigen detection was not restricted to tonsils, but was also detected in nasal cells from the olfactory region. In conclusion, palatine tonsils and adenoids are sites of prolonged infection by SARS-CoV-2 in children, even without COVID-19 symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.21.23284592v1" target="_blank">TONSILS ARE MAJOR SITES OF PROLONGED SARS-COV-2 INFECTION IN CHILDREN</a>
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<li><strong>Shielding under endemic SARS-CoV-2 conditions is easier said than done: a model-based analysis</strong> -
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As the COVID-19 pandemic continues unabated, many governments and public-health bodies worldwide have ceased to implement concerted measures for limiting viral spread, placing the onus instead on the individual. In this paper, we examine the feasibility of this proposition using an agent-based model to simulate the impact of individual shielding behaviors on reinfection frequency. We derive estimates of heterogeneity in immune protection from a population pharmacokinetic (pop PK) model of antibody kinetics following infection and variation in contact rate based on published estimates. Our results suggest that individuals seeking to opt out of adverse outcomes upon SARS-CoV-2 infection will find it challenging to do so, as large reductions in contact rate are required to reduce the risk of infection. Our findings suggest the importance of a multilayered strategy for those seeking to reduce the risk of infection. This work also suggests the importance of public health interventions such as universal masking in essential venues and air quality standards to ensure individual freedom of choice regarding COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284884v1" target="_blank">Shielding under endemic SARS-CoV-2 conditions is easier said than done: a model-based analysis</a>
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<li><strong>COVID-19 in Pakistan: A national analysis of five pandemic waves</strong> -
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Objectives The COVID-19 pandemic showed distinct waves where cases ebbed and flowed. While each country had slight, nuanced differences, lessons from each wave with country-specific details provides important lessons for prevention, understanding medical outcomes and the role of vaccines. This paper compares key characteristics from the five different COVID-19 waves in Pakistan. Methods We used specific criteria to define COVID-19 waves, and key variables such as COVID-19 tests, cases, and deaths with their rates of change to the peak and then to the trough were used to draw descriptive comparisons. Additionally, a linear regression model estimated daily new COVID-19 deaths in Pakistan. Results Pakistan saw five distinct waves, each of which displayed the typical topology of a complete infectious disease epidemic. The time from wave-start to peak became progressively shorter, and from wave-peak to trough, progressively longer. Each wave appears to also be getting shorter, except for wave 4, which lasted longer than wave 3. A one percent increase in vaccinations increased daily new COVID-19 deaths by 0.10% (95% CI: 0.01, 0.20) in wave 4 and decreased deaths by 0.38% (95% CI: -0.67, -0.08) in wave 5. Conclusion Each wave displayed distinct characteristics that must be interpreted in the context of the level of response and the variant driving the epidemic. Key indicators suggest that COVID-19 preventive measures kept pace with the disease. Waves 1 and 2 were mainly about prevention and learning how to clinically manage patients. Vaccination started late during Wave 3 and its impact became apparent on hospitalizations and deaths in Wave 5. The impact of highly virulent strains Alpha/B1.1.7 and Delta/B.1.617.2 variants during Wave 3 and milder but more infectious Omicron/BA.5.2.1.7 are apparent.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.23.23284902v1" target="_blank">COVID-19 in Pakistan: A national analysis of five pandemic waves</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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Phone satisfaction questionnaire<br/><b>Sponsor</b>: Centre Hospitalier René Dubos<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>Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Corfluvec component 1 low dose; Biological: Corfluvec component 2 low dose; Biological: Corfluvec component 1 high dose; Biological: Corfluvec component 2 high dose; Biological: Corfluvec low dose; Biological: Corfluvec high dose; Biological: Placebo<br/><b>Sponsors</b>: Tatyana Zubkova; MDP-CRO, LLC; St. Petersburg State Pavlov Medical 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>A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>: Shandong Provincial Hospital; Central hospital Affiliated to Shandong First Medical University; The Second Affiliated Hospital of Shandong First Medical University; The Affiliated Hospital Of Southwest Medical University; Gansu Provincial Hospital<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>A Chatbot to Enhance COVID-19 Knowledge</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: chatbot; Other: Printed educational booklet<br/><b>Sponsor</b>: Sun Yat-sen 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>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>: Jiangsu Cancer Institute & Hospital; Nanjing Chest Hospital; The Affiliated BenQ Hospital of Nanjing Medical University; Central South University; Zhongda Hospital<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>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tetrandrine<br/><b>Sponsor</b>: Peking University Third Hospital<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>A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>: Vitamin C; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Vitamin C; Drug: Placebo<br/><b>Sponsor</b>: Zhujiang Hospital<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>Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).<br/><b>Sponsor</b>: Hospital General Nuestra Señora del Prado<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 Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: DNA vaccine OC-007; Other: Placebo<br/><b>Sponsor</b>: Matti Sällberg<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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East Hospital<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>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Ousehold in China</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Huashan Hospital; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsor</b>: Peking Union Medical College Hospital<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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: UC-MSCs treatment<br/><b>Sponsors</b>: Shanghai East Hospital; Sir Run Run Shaw Hospital<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults</strong> - CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.</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 genetically encoded BRET-based SARS-CoV-2 M<sup>pro</sup> protease activity sensor</strong> - The main protease, M^(pro), is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting M^(pro) proteolytic activity in live cells as well as in vitro. The sensors were generated by sandwiching peptides containing the M^(pro) N-terminal…</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>Evaluation of a biotin-based surrogate virus neutralization test for detecting postvaccination antibodies against SARS-CoV-2 variants in sera</strong> - A severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) surrogate virus neutralization test (sVNT) was used to determine the degree of inhibition of binding between human angiotensin converting enzyme 2 (hACE2) and the receptor binding domain (RBD) of spike protein by neutralizing antibodies in a biosafety level 2 facility. Here, to improve the sensitivity and specificity of the commercial sVNT, we developed a new biotin based sVNT using biotinylated RBD and HRP conjugated streptavidin…</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>Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2</strong> - Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (M^(pro)) of SARS-CoV-2 as an example. We first…</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>Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling</strong> - Kruppel-like factor 2 (KLF2) has been linked with fibrosis and neutrophil-associated thromboinflammation; however, its role in COVID-19 remains elusive. We investigated the effect of disease microenvironment on the fibrotic potential of human lung fibroblasts (LFs) and its association with KLF2 expression. LFs stimulated with plasma from severe COVID-19 patients down-regulated KLF2 expression at mRNA/protein and functional level acquiring a pre-fibrotic phenotype, as indicated by increased…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 evolution influences GBP and IFITM sensitivity</strong> - SARS-CoV-2 spike requires proteolytic processing for viral entry. A polybasic furin-cleavage site (FCS) in spike, and evolution toward an optimized FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmission. Here we show interferon-inducible restriction factors Guanylate-binding proteins (GBP) 2 and 5 interfere with furin-mediated spike cleavage and inhibit the infectivity of early-lineage isolates Wuhan-Hu-1 and VIC. By contrast, VOCs Alpha and Delta escape…</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>Epitope-directed anti-SARS-CoV-2 scFv engineered against the key spike protein region could block membrane fusion</strong> - The newly emerged SARS-CoV-2 causing coronavirus disease (COVID-19) resulted in >500 million infections. A great deal about the molecular processes of virus infection in the host is getting uncovered. Two sequential proteolytic cleavages of viral spike protein by host proteases are prerequisites for the entry of the virus into the host cell. The first cleavage occurs at S1/S2 site by the furin protease, and the second cleavage at a fusion activation site, the S2’ site, by the TMPRSS2 protease….</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>Potent Dual Polymerase/Exonuclease Inhibitory Activities of Antioxidant Aminothiadiazoles Against the COVID-19 Omicron Virus: A Promising In Silico/In Vitro Repositioning Research Study</strong> - Recently, natural and synthetic nitrogenous heterocyclic antivirals topped the scene as first choices for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying disease, the coronavirus disease 2019 (COVID-19). Meanwhile, the mysterious evolution of a new strain of SARS-CoV-2, the Omicron variant and its sublineages, caused a new defiance in the continual COVID-19 battle. Hitting the two principal coronaviral-2 multiplication enzymes…</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>Neutralization activity of IgG antibody in COVID‑19‑convalescent plasma against SARS-CoV-2 variants</strong> - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the anti-SARS-CoV-2 antibody levels, anti-spike (S)-immunoglobulin G (IgG) and anti-nucleocapsid (N)-IgG, and the neutralization activity of IgG antibody in COVID‑19‑convalescent plasma against variants of SARS-CoV-2, alpha, beta, gamma, delta, kappa, omicron and R.1 strains. The study included 30 patients with clinically diagnosed COVID-19. The anti-S-IgG and anti-N-IgG…</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>Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective</strong> - Throughout the SARS-CoV-2 pandemic, the use of botanical dietary supplements in the United States has increased, yet their safety and efficacy against COVID-19 remains underexplored. The Quave Natural Product Library is a phylogenetically diverse collection of botanical and fungal natural product extracts including popular supplement ingredients. Evaluation of 1867 extracts and 18 compounds for virus spike protein binding to host cell ACE2 receptors in a SARS-CoV-2 pseudotyped virus system…</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>Potential Self-Peptide Inhibitors of the SARS-CoV-2 Main Protease</strong> - The SARS-CoV-2 main protease (M^(pro)) plays an essential role in viral replication, cleaving viral polyproteins into functional proteins. This makes M^(pro) an important drug target. M^(pro) consists of an N-terminal catalytic domain and a C-terminal α-helical domain (M^(pro)C). Previous studies have shown that peptides derived from a given protein sequence (self-peptides) can affect the folding and, in turn, the function of that protein. Since the SARS-CoV-1 M^(pro)C is known to stabilize 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>Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies</strong> - CONCLUSION: The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.</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 Enveloped Virus Surrogate Phi6 Infection Using Yeast-Derived Vacuoles</strong> - The periodic emergence of infectious disease poses a serious threat to human life. Among the causative agents, including pathogenic bacteria and fungi, enveloped viruses have caused global pandemics. In the last 10 years, outbreaks of severe acute respiratory syndrome coronavirus 2 disease, severe acute respiratory syndrome, and Middle East respiratory syndrome have all been caused by enveloped viruses. Among several paths of secondary transmission, inhalation of aerosols containing saliva with…</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>Valproate Coenzyme-A Conjugate Blocks Opening of Receptor Binding Domains in the Spike Trimer of SARS-CoV-2 through an Allosteric Mechanism</strong> - The receptor-binding domains (RBDs) of the SARS-CoV-2 spike trimer exhibit “up” and “down” conformations often targeted by neutralizing antibodies. Only in the “up” configuration can RBDs bind to the ACE2 receptor of the host cell and initiate the process of viral multiplication. Here, we identify a lead compound (3-oxo-valproate-coenzyme A conjugate or Val-CoA) that stabilizes the spike trimer with RBDs in the down conformation. Val-CoA interacts with three R408 residues, one from each RBD,…</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>Causal associations of tea intake with COVID-19 infection and severity</strong> - Tea ingredients can effectively inhibit SARS-CoV-2 infection at adequate concentrations. It is not known whether tea intake could impact the susceptibility to COVID-19 or its severity. We aimed to evaluate the causal effects of tea intake on COVID-19 outcomes. We performed Mendelian randomization (MR) analyses to assess the causal associations between tea intake (N = 441,279) and three COVID-19 outcomes, including SARS-CoV-2 infection (122,616 cases and 2,475,240 controls), hospitalized COVID-19…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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