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<title>29 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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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Increased Risk Perception, Distress Intolerance and Health Anxiety in Stricter Lockdowns: Self-Control as a Key Protective Factor in Early Response to the COVID-19 Pandemic</strong> -
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Studies provide evidence that distress, (health) anxiety and depressive symptoms were high during the first weeks of COVID-19 lockdown restrictions, decreasing over time, possibly due to individuals’ protective psychological factors. Relations between different lockdown restrictions, mental health issues, and protective factors need to be explored, since even small lockdown effects might increase the risk of future mental health issues. We merged objective lockdown stringency data with individual data (N = 1,001) to examine differences in lockdown effects in strict lockdown (Romania) and mild lockdown (Hungary) conditions between March and May 2020 on stressors and mental health symptoms, taking protective factors into account. The stricter lockdown in Romania revealed higher levels of perceived risk of infection, distress intolerance, and COVID-19 health anxiety. Protective psychological factors were not affected by the lockdown measures. Surpassing psychological flexibility and resilient coping, self-control proved to be the most promising protective factor. It is recommended that future research merge objective data with study data to investigate the effects of different COVID-19 lockdown measures on mental health and protective factors. Policy decisions should consider lockdown-dependent consequences of mental health issues. Intervention programs are suggested to mitigate mental health issues and to strengthen peoples’ protective psychological factors.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/ubfw2/" target="_blank">Increased Risk Perception, Distress Intolerance and Health Anxiety in Stricter Lockdowns: Self-Control as a Key Protective Factor in Early Response to the COVID-19 Pandemic</a>
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<li><strong>A psychological exploration into collecting behaviors during the COVID-19 pandemic</strong> -
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Over a third of Americans collect at least one type of item, with similar proportions found in other Western cultures. Despite the large size of the global population of collectors, little has been investigated in terms of collecting behaviors and their relationship with identity, compulsive buying, shopping addiction, mood modification, interpersonal relationships, spiritual aspects to collecting, and the differences between collectors. Cross-cultural research was used to investigate the aforementioned relationships and build a groundwork for future research. In addition, the impact of the COVID-19 pandemic on collecting behaviors was examined, with a focus on exploring the differences between people that greatly increased collection spending during the pandemic compared to those that did not or moderately increased their spending. High salience in collector identity was associated with higher levels of excessive buying, shopping addiction, mood modification, communal support for collecting, competitive collecting, relatedness with other collectors, viewing collecting as sacred/spiritual, and lower levels of doubt about collecting. Young and single collectors most drastically increased their spending during the COVID-19 pandemic, which led to higher levels of doubt, guilt, disgust, fear, loneliness, relationship strain, higher levels of dependence on collecting to modify mood, and higher levels of withdrawal symptoms consistent with addiction.
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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/fdm5a/" target="_blank">A psychological exploration into collecting behaviors during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Effect of Pranayama on Perceived Stress, Well Being and Quality of Life of Frontline Healthcare Professionals on Covid-19 Duty: A Quasi- Randomized Clinical Trial</strong> -
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Background The COVID-19 pandemic has brought unparalleled challenges for health systems worldwide, the impact of which has also been borne by the Healthcare Professionals (HCPs). Numerous studies have revealed the positive effects of Pranayama and Meditation on mental health. The effect of Pranayama in improving mental health of frontline HCP exposed to Covid-19 patients has not been studied. Aim & Objective: This quasi-randomized clinical trial was done to study the effect of especially designed Pranayama protocol on perceived stress, wellbeing and quality of life of frontline health care professionals who were exposed to COVID-19 patients in hospital settings. Methodology This study was done with 280 frontline healthcare professionals (HCP) assigned duties with COVID-19 patients during September-November, 2020 in 5 government hospitals and COVID-19 quarantine/isolation centres in New Delhi, India. The HCPs were first assessed for COVID-19 infection in the past using antibody test, and only those found negative were recruited. The enrolled respondents were randomly assigned to two arms an intervention arm where there were to practice 28 day Pranayama module (morning and evening sessions) under supervision of a trainer and a Control arm where the HCPs continued routine physical activity (walking jogging etc). Baseline and end-line (total: 250 HCPs) Psychological parameters of Perceived Stress, Well Being and Quality of Life were collected through self-reported questionnaires. Results The intervention (HCPs 123) and control (HCPs 127) groups (Total 250) were comparable in their demographic profile and baseline characteristics. Intervention with Pranayama module led to a significant reduction (Mean diff -2.46 P-value 0.028) in perceived stress score in the intervention group compared to the control group. The wellbeing index in Interventional group intervention showed a non-significant increase. The WHO Quality-of-life score increased in the intervention group as compared to the controls (mean difference 2.78, p-value: 0.17). Of its four components, the one for Psychological domain increased significantly (mean diff: 1.52, P-value: 0.019), while those for Physical domain and Environmental domains increased (mean diff: 0.64, P-value: 0.29 and mean diff: 0.68, p-value: 0.48) though not statistical significantly. Conclusion: The intervention of twice daily practice of the Pranayama module for 28 days in frontline HCPs performing COVID-19 duties had a noteworthy effect in lowering Perceived Stress, improving perceived Quality of life, especially its Psychological domains as measured through standardized questionnaires.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279201v1" target="_blank">Effect of Pranayama on Perceived Stress, Well Being and Quality of Life of Frontline Healthcare Professionals on Covid-19 Duty: A Quasi- Randomized Clinical Trial</a>
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<li><strong>Development and application of an uncapped mRNA platform</strong> -
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A novel uncapped mRNA platform was developed. Five lipid nanoparticle (LNP)-encapsulated mRNA constructs were made to evaluate several aspects of our platform, including transfection efficiency and durability in vitro and in vivo and activation of humoral and cellular immunity in several animal models. The constructs were eGFP-mRNA-LNP (for enhanced green fluorescence mRNA), Fluc-mRNA-LNP (for firefly luciferase mRNA), S{delta}T-mRNA-LNP (for Delta strain SARS-CoV-2 spike protein trimer mRNA), gDED-mRNA-LNP (for truncated glycoprotein D mRNA coding ectodomain from herpes simplex virus type 2 (HSV2)) and gDFR-mRNA-LNP (for truncated HSV2 glycoprotein D mRNA coding amino acids 1~400). Quantified target protein expression in vitro and in vivo was achieved with eGFP- and Fluc-mRNA-LNP. S{delta}T-mRNA-LNP, gDED-mRNA-LNP and gDFR-mRNA-LNP induced both humoral and cellular immune responses comparable to capped mRNA-LNP constructs reported previously. Notably, 25, 50 and 100 g of S{delta}T-mRNA-LNP elicited neutralizing antibodies in hamsters against the Omicron and Delta strains. Additionally, gDED-mRNA-LNP and gDFR-mRNA-LNP induced potent neutralizing antibodies in rabbits and mice. The mRNA constructs with uridine triphosphate (UTP) outperformed those with N1-methylpseudouridine triphosphate (N1m{psi}TP) in the in vivo expression of luciferase and induction of antibodies via S{delta}T-mRNA-LNP. Our uncapped, process-simplified, and economical mRNA platform may have broad uses in vaccines and protein replacement drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.05.494796v2" target="_blank">Development and application of an uncapped mRNA platform</a>
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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. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. 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/10.1101/2022.08.25.22279158v2" target="_blank">Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)</a>
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<li><strong>DeepLPI: a novel deep learning-based model for protein-ligand interaction prediction for drug repurposing</strong> -
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The substantial cost of new drug research and development has consistently posed a huge burden for both pharmaceutical companies and patients. In order to lower the expenditure and development failure rate, repurposing existing and approved drugs by identifying interactions between drug molecules and target proteins based on computational methods have gained growing attention. Here, we propose the DeepLPI, a novel deep learning-based model that mainly consists of ResNet-based 1-dimensional convolutional neural network (1D CNN) and bi-directional long short term memory network (biLSTM), to establish an end-to-end framework for protein-ligand interaction prediction. We first encode the raw drug molecular sequences and target protein sequences into dense vector representations, which go through two ResNet-based 1D CNN modules to derive features, respectively. The extracted feature vectors are concatenated and further fed into the biLSTM network, followed by the MLP module to finally predict protein-ligand interaction. We downloaded the well-known BindingDB and Davis dataset for training and testing our DeepLPI model. We also applied DeepLPI on a COVID-19 dataset for externally evaluating the prediction ability of DeepLPI. To benchmark our model, we compared our DeepLPI with the state-of-the-art methods of DeepCDA and DeepDTA, and observed that our DeepLPI outperformed these methods, suggesting the high accuracy of the DeepLPI towards protein-ligand interaction prediction. The high prediction performance of DeepLPI on the different datasets displayed its high capability of protein-ligand interaction in generalization, demonstrating that the DeepLPI has the potential to pinpoint new drug-target interactions and to find better destinations for proven drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.01.470868v2" target="_blank">DeepLPI: a novel deep learning-based model for protein-ligand interaction prediction for drug repurposing</a>
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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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🖺 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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<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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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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🖺 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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<li><strong>Fifteen Years of India’s NREGA: Employer of the Last Resort?</strong> -
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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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🖺 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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<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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🖺 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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<li><strong>Antimicrobial copper as an effective and practical deterrent to surface transmission of SARS-CoV-2</strong> -
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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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🖺 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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<li><strong>Living with “long COVID”: A systematic review and meta-synthesis of qualitative evidence</strong> -
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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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🖺 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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<li><strong>Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools</strong> -
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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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🖺 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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<li><strong>SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants</strong> -
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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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🖺 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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<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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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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🖺 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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<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 III (Immunobridging Study)</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>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>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Canadian Adaptive Platform Trial for Long COVID</strong> - <b>Condition</b>: Long COVID, Post COVID Condition, Post Acute Sequelae of COVID-19<br/><b>Interventions</b>: Drug: Ibudilast; Dietary Supplement: Whey Protein Isolate; Drug: Pentoxifylline; Other: Placebo<br/><b>Sponsor</b>: University Health Network, Toronto<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 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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</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>Anti-viral organic coatings for high touch surfaces based on smart-release, Cu<sup>2+</sup> containing pigments</strong> - Viruses such as SARS-CoV-2 can remain viable on solid surfaces for up to one week, hence fomites are a potential route of exposure to infectious virus. Copper has well documented antiviral properties that could limit this problem, however practical deployment of copper surfaces has been limited due to the associated costs and the incompatibility of copper metal in specific environments and conditions. We therefore developed an organic coating containing an intelligent-release Cu^(2+) pigment…</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 motivations and their conditions which drive students to seek higher education in a foreign country</strong> - This article summarizes a vast literature tracing the plethora of motivations of international students to study abroad. We detail the push factors (i.e., personal goals) and pull factors (i.e., attracting elements) for this decision to pursue higher education overseas. To elaborate, the push factors are around the attainment and/or increase of three main capitals: human, financial and psychological. Pull factors are around the attracting capacity of three main entities: the destination country,…</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 mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics</strong> - CONCLUSION: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.</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>Complanatuside alleviates inflammatory cell damage induced by pro-inflammatory cytokines in skin keratinocytes</strong> - Cytokine-mediated inflammatory response is considered a cause of skin lesion in COVID-19 patients. Complanatuside is a flavonol glycoside isolated from Astragalus complanatus. Flavonoids from Astragalus complanatus were reported to have anti-inflammatory and anticancer activities but the potential protective effect of complanatuside on cytokine-induced inflammatory damage in skin keratinocytes is not known. The aim of this study is to explore the inhibitory effect of complanatuside on…</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>Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review</strong> - Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal…</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>Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones</strong> - Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV-Vis, IR, ¹H NMR, ^(13)C NMR, ^(15)N NMR and melting point determination. Optimized molecular structures, UV-Vis and IR spectra modeling, 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>Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</strong> - Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure…</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-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity</strong> - The current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and immune-persistence of the CoronaVac or Covilo inactivated COVID-19 Vaccine: a 6-month population-based cohort study</strong> - CONCLUSION: Antibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19…</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>Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients</strong> - CONCLUSIONS: We discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.</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>Papain-like protease of SARS-CoV-2 inhibits RLR signaling in a deubiquitination-dependent and deubiquitination-independent manner</strong> - The newly emerged severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can result in dysregulated interferon (IFN) responses that contribute to disease severity. The papain-like protease of SARS-CoV-2 (SCoV2-PLpro) has been previously reported to attenuate IFN responses, but the underlying mechanism is not fully understood. In this study, we found that SCoV2-PLpro potently suppressed IFN production and signaling induced by Sendai virus as well as RIG-I-like receptor (RLR)…</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>Ginsenoside Rg5 allosterically interacts with P2RY<sub>12</sub> and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory response</strong> - CONCLUSIONS: Rg5 could attenuate experimental DVT by counteracting NETosis and inflammatory response in neutrophils via P2RY(12), which may pave the road for its clinical application in the prevention of DVT-related disorders.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural inhibitors of SARS-CoV-2 main protease: structure based pharmacophore modeling, molecular docking and molecular dynamic simulation studies</strong> - Main protease (M^(pro)) plays a key role in replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was designed for finding natural inhibitors of SARS-CoV-2 M^(pro) by in silico methods. To this end, the co-crystal structure of M^(pro) with telaprevir was explored and receptor-ligand pharmacophore models were developed and validated using pharmit. The database of “ZINC Natural Products” was screened, and 288 compounds were filtered according to pharmacophore…</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 MEK signaling prevents SARS-CoV2-induced lung damage and improves survival of infected mice</strong> - Coronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with 6 million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID-19-caused death, effective medication to relieve COVID-19-associated symptoms and alleviate disease progression is still in high demand. In particular, one in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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