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186 lines
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<title>28 August, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges A Systematic Review Protocol</strong> -
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Introduction Health system resilience is the ability to prepare, manage, and learn from a sudden and unpredictable extreme change which impacts health systems. Health systems globally have recently been affected by a number of catastrophic events, including natural disasters, and infectious disease epidemics. Understanding health system resilience has never been more essential until emerging global pandemics. Therefore, the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic. Methodology The systematic review will be reported using the Preferred reporting items for systematic review and meta-analysis protocols guideline (PRISMA-P). Reporting data on health system building blocks and systematic searches on resilience enhancing strategies for the management of Public Health Emergencies of International Concerns (PHEIC) after the establishment of International Health Regulations (IHR) since managing PHEIC after the establishment of IHR in 2007 will be included. The search will be conducted in PubMed, Scopus, Web of Science, Google Scholar, and grey literature. Discussion Health system resilience is key to coping with catastrophic events, such as the economic crisis and COVID-19 pandemic. The mapping of available literature towards the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic to improve the level of preparedness and response to similar public health emergencies in the future. Conclusion A protocol for a global review of health system resilience for pandemic management is described. This review will add to the body of knowledge about health systems enhancing research and policy formulation.
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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/10.1101/2022.06.14.22276386v3" target="_blank">Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges A Systematic Review Protocol</a>
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</div></li>
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<li><strong>Evidence from 35 countries that the social perception of key protagonists is associated with containment measures during the COVID-19 pandemic</strong> -
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<div>
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It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from six continents during the COVID-19 pandemic that the social perception of key protagonists on two basic dimensions of social perception – warmth and competence – played a crucial role in shaping pandemic-related behaviors. Firstly, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, the social perception of these and other protagonists differed significantly within and between countries across warmth and competence. Thirdly, warmth and competence perceptions of heads of state, physicians, and protest movements translated into support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global 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/8xgb5/" target="_blank">Evidence from 35 countries that the social perception of key protagonists is associated with containment measures during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Fifteen Years of India’s NREGA: Employer of the Last Resort?</strong> -
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<div>
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For the last decade, India’s National Rural Employment Guarantee Act (NREGA, 2005) has been the world’s largest public works programme. This legal entitlement provided employment to 28 percent of rural Indian households in 2019-20. After the COVID-19 pandemic, NREGA is increasingly emerging as an invaluable employer of the last resort. However, longitudinal data of its implementation in the last fifteen years reveals distinctive trends. On the one hand, since inception NREGA has rendered greater benefit to women and marginalised communities. But on the other, since 2014, the right-wing Bharatiya Janata Party (BJP)-led government has reduced NREGA coverage compared to its implementation during the previous Indian National Congress (INC)-led United Progressive Alliance (UPA) coalition which had enacted the legislation. Nevertheless, in light of the pandemic and based on from international experiences, there is an urgent need for expansion of the employment guarantee.
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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/92un7/" target="_blank">Fifteen Years of India’s NREGA: Employer of the Last Resort?</a>
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</div></li>
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<li><strong>Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis</strong> -
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Background: Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers due to the restricted length of observational time, nor the shared genetic influences underlying these conditions. Methods: Leveraging summary statistics from the hitherto largest genome-wide association studies conducted in each trait, we performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture and the putative genetic associations between COVID-19 with three main female-specific cancers: breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC). Three phenotypes were selected to represent COVID-19 susceptibility (SARS-CoV-2 infection) and severity (COVID-19 hospitalization, COVID-19 critical illness). Results: For COVID-19 susceptibility, we found no evidence of a genetic correlation with any of the female-specific cancers. For COVID-19 severity, we identified a significant genome-wide genetic correlation with EC for both hospitalization (r_g=0.19, P=0.01) and critical illness (r_g=0.29, P=3.00*10-4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (ORIVW=1.09, 95%CI=1.01-1.18, P=0.04) and critical illness (ORIVW=1.06, 95%CI=1.00-1.11, P=0.04) with EC risk, none withstanding multiple correction. No reverse association was found. Cross-trait meta-analysis identified multiple pleiotropic SNPs between COVID-19 and female-specific cancers, including 20 for BC, 15 for EOC, and 5 for EC. Transcriptome-wide association studies revealed shared genes, mostly enriched in the hematologic, cardiovascular, and nervous systems. Conclusions: Our genetic analysis highlights an intrinsic link underlying female-specific cancers and COVID-19 - while COVID-19 is not likely to elevate the immediate risk of the examined female-specific cancers, it appears to share mechanistic pathways with these conditions. These findings may provide implications for future therapeutic strategies and public health actions.
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</p>
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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.medrxiv.org/content/10.1101/2022.08.25.22279195v1" target="_blank">Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis</a>
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</div></li>
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<li><strong>Antimicrobial copper as an effective and practical deterrent to surface transmission of SARS-CoV-2</strong> -
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<div>
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The aerosols are critical for SARS-CoV-2 transmission, however in areas with high confluence of people the contaminated surfaces take an important role that we could attack using antimicrobial surfaces including copper. In this study, we wanted to challenge infectious SARS-CoV-2 with two samples of copper surfaces and one plastic surface as control at different direct times contact. To evaluate and quantify virucidal activity of copper against SARS-CoV-2, two methods of experimental infection were performed, TCID50 and plaque assays on VeroE6 cells, showing significant inactivation of high titer of SARS-CoV-2 within minutes reaching 99.9 % of inactivation of infectivity on both copper surfaces. Daily high demand surfaces contamination is an issue that we have to worry about not only during the actual pandemic time but also for future, where copper or its alloys will have a pivotal role.
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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/10.1101/2022.08.25.505365v1" target="_blank">Antimicrobial copper as an effective and practical deterrent to surface transmission of SARS-CoV-2</a>
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</div></li>
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<li><strong>Living with “long COVID”: A systematic review and meta-synthesis of qualitative evidence</strong> -
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<div>
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Objectives: Long-term health consequences of coronavirus disease (COVID-19), also known as “long COVID,” has become a global health concern. In this systematic review, we aimed to synthesize the qualitative evidence on lived experiences of people living with long COVID that may inform health policymaking and practice. Methods: We searched six major databases and additional sources and systematically retrieved relevant qualitative studies and conducted a meta-synthesis of key findings using the Joanna Briggs Institute (JBI) guidelines and reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. Results: We found 15 articles representing 12 studies out of 619 citations from different sources. These studies provided 133 findings that were categorized into 55 categories. All categories were aggregated to the following synthesized findings: living with complex physical health problems, psychosocial crises of long COVID, slow recovery and rehabilitation, digital resources and information management, changes in social support, and experiences with healthcare providers, services, and systems. Ten studies were from the UK, and others were from Denmark and Italy, which highlights a critical lack of evidence from other countries. Conclusions: More representative research is needed to understand long COVID-related experiences from diverse communities and populations. The available evidence informs a high burden of biopsychosocial challenges among people with long COVID that would require multilevel interventions such as strengthening health and social policies and services, engaging patients and caregivers in making decisions and developing resources, and addressing health and socioeconomic disparities associated with long COVID through evidence-based practice.
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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/r7gxu/" target="_blank">Living with “long COVID”: A systematic review and meta-synthesis of qualitative evidence</a>
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</div></li>
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<li><strong>Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools</strong> -
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<div>
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Quantifying SARS-like coronavirus (SL-CoV) evolution is critical to understanding the origins of SARS-CoV-2 and the molecular processes that could underlie future epidemic viruses. While genomic evidence implicates recombination as a factor in the emergence of SARS-CoV-2, few studies have quantified recombination rates among SL-CoVs. Here, we infer recombination rates of SL-CoVs from correlated substitutions in sequencing data using a coalescent model with recombination. Our computationally-efficient, non-phylogenetic method infers recombination parameters of both sampled sequences and the unsampled gene pools with which they recombine. We apply this approach to infer recombination parameters for a range of positive-sense RNA viruses. We then analyze a set of 191 SL-CoV sequences (including SARS-CoV-2) and find that ORF1ab and S genes frequently undergo recombination. We identify which SL-CoV sequence clusters have recombined with shared gene pools, and show that these pools have distinct structures and high recombination rates, with multiple recombination events occurring per synonymous substitution. We find that individual genes have recombined with different viral reservoirs. By decoupling contributions from mutation and recombination, we recover the phylogeny of non-recombined portions for many of these SL-CoVs, including the position of SARS-CoV-2 in this clonal phylogeny. Lastly, by analyzing 444,145 SARS-CoV-2 whole genome sequences, we show current diversity levels are insufficient to infer the within-population recombination rate of the virus since the pandemic began. Our work offers new methods for inferring recombination rates in RNA viruses with implications for understanding recombination in SARS-CoV-2 evolution and the structure of clonal relationships and gene pools shaping its origins.
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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/10.1101/2022.08.26.505425v1" target="_blank">Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools</a>
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</div></li>
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<li><strong>SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants</strong> -
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<div>
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ABSTRACT Objectives: In our previous research, we have reported mathematical model with molecular simulation analysis to predict the infectivity of seven SARS-CoV-2 variants. In this report, we aimed to predict the relative risk of the recent new variants of SARS-CoV-2 based on our previous research. Methods: We subjected Omicron BA.4/5 or BA.2.75 variant of SARS-CoV-2 to the analysis for the evolutionary distance of the spike protein gene (S gene) to appreciate the changes of the spike protein. We performed the molecular docking simulation analyses of the spike protein with human angiotensin-converting enzyme 2 (ACE2) to understand the docking affinity in these variants. We then compared the evolutionary distance and the docking affinity of these variants with that of the seven variants which were analyzed in our previous research. Results: The evolutionary distance of the S gene in BA.4/5 or BA.2.75 from the Wuhan variant were longer than the other variants. The highest docking affinity of the spike protein with ACE2 (ratio per Wuhan variant) was observed in BA.2.75. Conclusion: It is important to note that BA.2.75 has both the highest docking affinity and the longest evolutionary distance of the S gene. These results suggest that the infection of BA.2.75 can be spread further than preexisting variants.
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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/10.1101/2022.08.25.505217v1" target="_blank">SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants</a>
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</div></li>
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<li><strong>Enhancer deregulation in TET2 Mutant Clonal Hematopoiesis is associated with increased COVID-19 related inflammation severity and mortality</strong> -
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<div>
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Coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. It remains unclear which factors determine severity of illness and long-term outcomes. Emerging evidence points towards an important role of preexisting host factors, such as a deregulated inflammatory response at the time of infection. Here, we demonstrate the negative impact of clonal hematopoiesis, a prevalent clonal disorder of ageing individuals, on COVID-19-related cytokine release severity and mortality. We show that mutations in the gene coding for the methylcytosine dioxygenase TET2 promotes amplification of classical and intermediate monocyte subsets. Using single cell multiomic sequencing approaches, we identify cell-specific gene expression changes associated with the loss of TET2 and significant epigenomic deregulation affecting enhancer accessibility of a subset of transcription factors involved in monocyte differentiation. We further identify EGR1 down-regulation secondary to TET2-mediated hypermethylation, resulting in overexpression of MALAT1, a lncRNA that plays a role in hematopoietic stem cell differentiation and monocyte lineage commitment. Together, these data provide a mechanistic insight to the poor prognostic value of clonal hematopoiesis in patients infected with Sars-COV2.
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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/10.1101/2022.08.25.505316v1" target="_blank">Enhancer deregulation in TET2 Mutant Clonal Hematopoiesis is associated with increased COVID-19 related inflammation severity and mortality</a>
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<li><strong>Predicting the efficacy of variant-modified COVID-19 vaccine boosters</strong> -
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As a result of the emergence and circulation of antigenically distinct SARS-CoV-2 variants, a number of variant-modified COVID-19 vaccines have been developed. Here we perform a meta-analysis of the available data on neutralisation titres from clinical studies comparing booster vaccination with either the current ancestral-based vaccines or variant-modified vaccines. We then use this to predict the relative efficacies of these booster vaccines under different scenarios.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279237v1" target="_blank">Predicting the efficacy of variant-modified COVID-19 vaccine boosters</a>
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<li><strong>Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps</strong> -
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The disinfection of air using Germicidal Ultraviolet light (GUV) is a long-standing technique, which has received intense attention during the COVID-19 pandemic. GUV generally uses UVC lamps as its light source, which are known to initiate photochemistry in air. However, the impact of GUV on indoor air quality and chemistry has not been investigated in detail, to our knowledge. In this study, we model the chemistry initiated by GUV at 254 or 222 nm (“GUV254” or “GUV222”) in a typical room with typical indoor pollutant levels, and for different ventilation levels. GUV254 is irritating for skin and eyes, has an occupational exposure limit, and thus these fixtures typically irradiate a smaller volume near the ceiling, or inside ventilation ducts. In contrast, GUV222 is described by some as harmless to skin or eyes due to rapid absorption in a very thin external layer. Our analysis showed that GUV254 is able to significantly photolyze O3, generating OH radicals, which initiates the oxidation of all indoor volatile organic compounds (VOCs). While secondary organic aerosol (SOA) can be formed as a product of VOC oxidation, most of SOA in our case studies is produced through GUV-independent terpene ozonolysis. GUV254-induced SOA formation is of the order of 0.1-1 μg m-3. GUV222 with the same effective virus removal rate makes a smaller impact on indoor air quality, mainly because of the significantly lower UV irradiance needed and substantially less efficient O3 photolysis (for primary OH generation) than at 254 nm.
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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/10.1101/2022.08.25.22279238v1" target="_blank">Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps</a>
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<li><strong>International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship</strong> -
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Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279181v1" target="_blank">International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship</a>
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<li><strong>Mortality Improvements in Adult Patients Hospitalised with Community Acquired COVID-19 in Wales From March 2020 to Decemeber 2021</strong> -
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Background A COVID-19 hospital guideline was implemented across all acute hospitals in Wales in March 2020, and data was collected across the first 3 Waves of the pandemic. We aimed to observe trends in mortality with a focus on ward-based outcomes. Methods Retrospective case-note review of data for adults admitted to hospital with community acquired COVID-19 between March 2020 and December 2021 Results 5887 cases were analysed. Overall mortality from COVID-19 fell from 31.5% in Wave 1 to 22.6% in Wave 2 to 18.8% in Wave 3 (p<0.01). Ward mortality for patients on oxygen fell from 34.6% in Wave 1 to 19.5% in Wave 2 (p<0.01) to 14.3% in Wave 3 (p=0.03). For those managed with CPAP/HFNO on wards, the mortality reduced from 58.9% in Wave 1 to 45.6% in Wave 2 (p=0.05) and further to 42.6% in Wave 3 (p=0.03). The mortality for patients managed with CPAP/HFNO on ICU reduced from 43.8% in Wave 1 to 24.7% in Wave 2 (p=0.12) and further to 20.4% in Wave 3 (p=0.03). Patients receiving CPAP/HFNO on the wards were on average 11 years older and more co-morbid than those on ICU. In Wave 3, 77% of hospital admissions with COVID-19 were unvaccinated with mortality rates of 20.5% compared to 4.8% mortality in those who had received three vaccines (p<0.01). Conclusions There were successive reductions in mortality in inpatients over the 3 Waves reflecting new treatments and better management of complications. The impact of vaccines on outcomes of hospitalised patients was notable in Wave 3.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.26.22279219v1" target="_blank">Mortality Improvements in Adult Patients Hospitalised with Community Acquired COVID-19 in Wales From March 2020 to Decemeber 2021</a>
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</div></li>
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<li><strong>Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)</strong> -
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Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac (“CC-C”, n=101) or BNT162b2 (“CC-B”, n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac (“BB-C”, n=118) or BNT162b2 (“BB-B”, n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279158v1" target="_blank">Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)</a>
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<li><strong>Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity to decreasing COVID-19 vaccine effectiveness during alpha and delta variant waves</strong> -
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Background: The decline in COVID-19 mRNA vaccine effectiveness (VE) is well established, however the impact of variant-specific immune evasion and waning protection remains unclear. Here, we use whole-genome-sequencing (WGS) to tease apart the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluate the utility of calendar-period-based variant classification as an alternative to WGS. Methods: We conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and secondarily by calendar-period. We estimated VE as one minus the ratio comparing the odds of infection among vaccinated and unvaccinated people. Results: Overall, 2,029 cases (RT-PCR positive, sequenced samples) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha infection (84.4%, 95% confidence interval: 75.6-90.0%) than Delta infection (68.9%, CI: 58.0-77.1%, p-value: 0.013). The odds of WGS-classified Delta infection were significantly higher 90-149 than 14-89 days after 2nd dose (Odds ratio: 1.6, CI: 1.2-2.3). While estimates of VE against calendar-period-classified infections approximated estimates against WGS-classified infections, calendar-period-based classification was subject to outcome misclassification (35% during Alpha period, 4% during Delta period). Conclusions: These findings suggest that both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While estimates of VE against calendar-period-classified infections mirrored that against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely.
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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/10.1101/2022.08.25.22278443v1" target="_blank">Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity to decreasing COVID-19 vaccine effectiveness during alpha and delta variant 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>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SIM0417; Drug: Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<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>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>: University of Manitoba<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>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<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>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo<br/><b>Sponsors</b>: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>: LumiraDx UK Limited<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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)<br/><b>Sponsors</b>: The Aurum Institute NPC; Coalition for Epidemic Preparedness Innovations<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 Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., Ltd.<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>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<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>UNAIR Inactivated COVID-19 Vaccine Phase 3</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<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>Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19; AMS-H-03; Hydrogen-oxygen Gas<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment<br/><b>Sponsor</b>: Shanghai Zhongshan 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>Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Child, Only<br/><b>Intervention</b>: Drug: Jinzhen oral liquid or Jinhuaqinggan granules<br/><b>Sponsor</b>: The Affiliated Hospital of Qingdao University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study</strong> - <b>Conditions</b>: COVID-19; Kidney Transplant<br/><b>Intervention</b>: Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); PPD; Johns Hopkins University; Sanofi Pasteur, a Sanofi Company<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>Smartphone Intervention for Overdose and COVID-19</strong> - <b>Conditions</b>: Substance Use Disorders; Overdose; COVID-19<br/><b>Intervention</b>: Device: iThrive WI Intervention<br/><b>Sponsors</b>: University of Wisconsin, Madison; National Institute on Drug Abuse (NIDA)<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>Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019</strong> - <b>Condition</b>: Coronavirus Disease 2019<br/><b>Interventions</b>: Drug: Huashi Baidu granule; Drug: compound pholcodine oral solution<br/><b>Sponsor</b>: Shanghai Children’s Medical Center<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Are herbal-peptides effective as adjunctive therapy in Coronavirus disease COVID-19?</strong> - CONCLUSION: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.</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 favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms</strong> - The proceeding pandemic of coronavirus disease 2019 is the latest global challenge. Like most other infectious diseases, inflammation, oxidative stress, and immune system dysfunctions play a pivotal role in the pathogenesis of COVID-19. Furthermore, the quest of finding a potential pharmaceutical therapy for preventing and treating COVID-19 is still ongoing. Silymarin, a mixture of flavonolignans extracted from the milk thistle, has exhibited numerous therapeutic benefits. We reviewed 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>IMMUNE DYSREGULATION INDUCED BY SPIKE PROTEIN 1 OF SARS-COV-2 INCREASES ENDOTHELIAL CELL DYSFUNCTION VIA TYPE I AND TYPE III INTERFERON ACTIVATION PATHWAYS</strong> - CONCLUSIONS: In ECs, S1P, IFNα and IFNL3 increased ISG15 and IL-6, processes that involve ADAM17. Inflammation induced by S1P was amplified by IFNs. IFNs induce vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This is especially important in the presence of cardiovascular risk factors, including hypertension.</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>PREVENTIVE EFFECT OF STATINS AGAINST RESPIRATORY TRACT INFECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS</strong> - CONCLUSIONS: The findings of our systematic review and meta-analysis do not support the hypothesis that statins reduce the risk of including RTIs.</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>Establishment of Neutralizing Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 by the Screening with Exosomes Expressing the Viral Spike Protein</strong> - Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, are the important tools both for the diagnosis and therapeutics of this infectious disease. The high-performance antibody against spike protein of SARS-CoV-2 is expected to inhibit the binding of viruses to their receptors on the surface of their target cells. In this study, we propose the novel screening method for mAbs against the pathogenic infectious virus using exosome….</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>IMPAIRED BETA-2ADRENERGIC ENDOTHELIUM-DEPENDENT VASODILATION IS REVERSED BY PHOSPHODIESTERASE INHIBITION IN PATIENTS PREVIOUSLY HOSPITALIZED WITH COVID-19</strong> - CONCLUSIONS: In subjects previously hospitalized with severe COVID-19, endothelial function is impaired for many months after hospital discharge and the impaired NO-cGMP mediated vasodilation may be reversed by sildenafil.</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>Advances in cell death mechanisms involved in viral myocarditis</strong> - Viral myocarditis is an acute inflammatory disease of the myocardium. Although many etiopathogenic factors exist, coxsackievirus B3 is a the leading cause of viral myocarditis. Abnormal cardiomyocyte death is the underlying problem for most cardiovascular diseases and fatalities. Various types of cell death occur and are regulated to varying degrees. In this review, we discuss the different cell death mechanisms in viral myocarditis and the potential interactions between them. We also explore…</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>Dynamicity and persistence of severe acute respiratory syndrome coronavirus-2 antibody response after double dose and the third dose with BBV-152 and AZD1222 vaccines: A prospective, longitudinal cohort study</strong> - CONCLUSION: This year-long follow-up study found a 7- and 5-fold antibody waning in Covaxin and Covishield recipients, respectively, without any breakthrough infection history. However, individuals with booster breakthrough had mild symptoms and did not require hospital admission. The data also indicate the possible escape of omicron variants despite the presence of vaccine-induced neutralizing 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>Exploring the Impact of ACE Inhibition in Immunity and Disease</strong> - Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must…</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>Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development</strong> - COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit 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>Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection</strong> - Porcine deltacoronavirus (PDCoV) is a recently discovered enteropathogenic coronavirus and has caused significant economic impacts on the pork industry. Although studies have partly uncovered the molecular mechanism of PDCoV-host interaction, it requires further research. In this study, we explored the roles of Stromal Antigen 2 (STAG2) in PDCoV infection. We found that STAG2-deficient cells inhibited infection with vesicular stomatitis virus (VSV) and PDCoV, whereas restoration of STAG2…</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>Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication</strong> - DNA damage response (DDR) is an evolutionarily conserved mechanism by which eukaryotic cells sense DNA lesions caused by intrinsic and extrinsic stimuli, including virus infection. Although interactions between DNA viruses and DDR have been extensively studied, how RNA viruses, especially coronaviruses, regulate DDR remains unknown. A previous study showed that the porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the Coronaviridae family, induces DDR in infected…</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>Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro</strong> - Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between 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>Evaluation of Novel Guanidino-Containing Isonipecotamide Inhibitors of Blood Coagulation Factors against SARS-CoV-2 Virus Infection</strong> - Coagulation factor Xa (fXa) and thrombin (thr) are widely expressed in pulmonary tissues, where they may catalyze, together with the transmembrane serine protease 2 (TMPRSS2), the coronaviruses spike protein (SP) cleavage and activation, thus enhancing the SP binding to ACE2 and cell infection. In this study, we evaluate in vitro the ability of approved (i.e., dabigatran and rivaroxaban) and newly synthesized isonipecotamide-based reversible inhibitors of fXa/thr (cmpds 1-3) to hinder 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>Anti-Spike and Neutralizing Antibodies after Two Doses of COVID-19 Sinopharm/BIBP Vaccine</strong> - Host response to COVID-19 vaccines is partially evaluated through the estimation of antibody response, specifically the binding anti-spike (anti-S) and the neutralizing antibodies (nAbs) against SARS-CoV-2. Vaccine-induced humoral response affects decisions on the choice of vaccine type, vaccine acceptance, and the need for boosting. Identification of risk factors for poor antibody response helps to stratify individuals who might potentially require booster doses. The primary objective of this…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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