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184 lines
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<title>07 September, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p</strong> -
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RNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556164v1" target="_blank">Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p</a>
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<li><strong>A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</strong> -
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During the COVID-19 pandemic, many countries and regions investigated the potential use of wastewater-based disease surveillance as an early warning system. Initially, methods were created to detect the presence of SARS-CoV-2 RNA in wastewater. Investigators have since conducted extensive studies to examine the link between viral concentration in wastewater and COVID-19 cases in areas served by sewage treatment plants over time. However, only a few reports have attempted to create predictive models for hospitalizations at county-level based on SARS-CoV-2 RNA concentrations in wastewater. This study implemented a linear mixed-effects model that observes the association between levels of virus in wastewater and county-level hospitalizations. The model was then utilized to predict short-term county-level hospitalization trends in 21 counties in California based on data from March 21, 2022, to May 21, 2023. The modeling framework proposed here permits repeated measurements as well as fixed and random effects. The model that assumed wastewater data as an input variable, instead of cases or test positivity rate, showed strong performance and successfully captured trends in hospitalizations. Additionally, the model allows for the prediction of SARS-CoV-2 hospitalizations two weeks ahead. Forecasts of COVID-19 hospitalizations could provide crucial information for hospitals to better allocate resources and prepare for potential surges in patient numbers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.14.23293945v2" target="_blank">A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</a>
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</div></li>
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<li><strong>COVFlow: phylodynamics analyses of viruses from selected SARS-CoV-2 genome sequences</strong> -
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Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.17.496544v7" target="_blank">COVFlow: phylodynamics analyses of viruses from selected SARS-CoV-2 genome sequences</a>
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</div></li>
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<li><strong>Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors</strong> -
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We report the results of the COVID Moonshot, a fully open-science, crowd sourced, structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a non-covalent, non-peptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV- 2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>840 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.10.29.339317v5" target="_blank">Open Science Discovery of Potent Non-Covalent SARS-CoV-2 Main Protease Inhibitors</a>
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</div></li>
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<li><strong>Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals</strong> -
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Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine to reduce reactogenicity, and an updated receptor-binding domain derived from Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N=96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with a lower frequency of adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23294493v1" target="_blank">Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals</a>
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</div></li>
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<li><strong>Cluster-level spillover randomized controlled trial to assess the impact of monetary incentives on COVID-19 vaccination uptake</strong> -
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<div>
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To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccination—by 15.3 percentage points on average—the same financial incentive yielded a precisely estimated null effect on vaccination. We discuss when financial incentives are most likely to fail, and conclude that it is critical to educate policy makers on the potential pitfalls of employing financial incentives to promote contributions to public goods.
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🖺 Full Text HTML: <a href="https://osf.io/jq28n/" target="_blank">Cluster-level spillover randomized controlled trial to assess the impact of monetary incentives on COVID-19 vaccination uptake</a>
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<li><strong>Serological outcomes of SARS-CoV-2 infection by vaccination status and variant in England</strong> -
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Background Throughout the SARS–CoV–2 pandemic, several vaccines have been rolled out and distinct variants with different severity and immune profiles emerged in England. Using data from enhanced surveillance of COVID-19 in vaccine eligible individuals we investigated the antibody response following SARS–CoV–2 infection according to vaccination status and variant. Methods PCR–positive eligible individuals were identified from community PCR testing data in England between February 2021 and April 2022 and contacted by nurses to complete questionnaires at recruitment and 21 days post recruitment. Individuals were sent self–sampling kits and self–sampled nasal/oropharyngeal swabs were taken day 1, day 3 and day 7 post–recruitment as well as acute (day 1), convalescent (follow–up) serum and oral fluid samples. Regression analyses were used to investigate how N antibody seroconversion differs by vaccine status, and to investigate how N and S antibody levels differ by vaccine status overall and stratified by variants. Interval–censored analyses and regression analyses were used to investigate the effect of acute S antibody levels on the duration of positivity, the cycle threshold values, the self–reported symptom severity and the number of symptoms reported. Results A total of 1,497 PCR positive individuals were included. A total of 369 (24.7%) individuals were unvaccinated, 359 (24.0%) participants were infected with Alpha, 762 (50.9%) with Delta and 376 (25.2%) with Omicron. The median age of participants was 49 years old (IQR 39–57). Convalescent anti–N antibody levels were lower in vaccinated individuals and convalescent anti–S antibody levels were higher in vaccinated individuals and increased with the number of doses received. Acute anti–S antibody level increased with the number of doses received. Higher acute anti–S antibody levels were associated with a shorter duration of positivity (overall and for the Delta variant). Higher acute anti–S antibody levels were also associated with higher Ct values (overall and for the Alpha and Delta variants). There was no association between the acute anti–S antibody level and self–reported symptom severity. Individuals with higher acute anti–S antibody level were less likely to report six or more symptoms (overall and for Delta variant). Conclusion Understanding the characteristics of the antibody response, its dynamics over time and the immunity it confers is important to inform future vaccination strategies and policies. Our findings suggest that vaccination is associated with high acute anti–S antibody level but reduced convalescent anti–N antibody level. High anti–S antibody level is associated with reduced duration of infection, reduced infectiousness and may also be associated with reduced symptoms severity and number of symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.05.23295073v1" target="_blank">Serological outcomes of SARS-CoV-2 infection by vaccination status and variant in England</a>
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<li><strong>IMPACT OF THE COVID-19 PANDEMIC ON ROUTINE HIV CARE AND ANTIRETROVIRAL TREATMENT OUTCOMES IN KENYA: A NATIONALLY REPRESENTATIVE ANALYSIS</strong> -
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Background: The COVID-19 pandemic adversely disrupted global health service delivery. We aimed to assess impact of the pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and initial virologic non-suppression (VnS) among individuals starting antiretroviral therapy (ART) in Kenya. Methods: Individual-level longitudinal service delivery data were analysed. Random sampling of individuals aged >15 years starting ART between April 2018 - March 2021 was done. Date of ART initiation was stratified into pre-COVID-19 (April 2018 - March 2019 and April 2019 - March 2020) and COVID-19 (April 2020 - March 2021) periods. Mixed effects generalised linear, survival and logistic regression models were used to determine the effect of COVID-19 pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and VnS, respectively. Results: Of 7,046 individuals sampled, 35.5%, 36.0% and 28.4% started ART during April 2018 - March 2019, April 2019 - March 2020 and April 2020 - March 2021, respectively. Compared to the pre-COVID-19 period, the COVID-19 period had higher same-day HIV diagnosis/ART initiation (adjusted risk ratio [95% CI]: 1.09 [1.04-1.13], p<0.001) and lower six-months non-retention (adjusted hazard ratio [95% CI]: 0.66 [0.58-0.74], p<0.001). Of those sampled, 3,296 (46.8%) had a viral load test done at a median 6.2 (IQR, 5.3-7.3) months after ART initiation. Compared to the pre-COVID-19 period, there was no significant difference in VnS during the COVID-19 period (adjusted odds ratio [95% CI]: 0.79 [95% CI: 0.52-1.20], p=0.264). Conclusions: In the short term, the COVID-19 pandemic did not have an adverse impact on HIV care and treatment outcomes in Kenya. Timely, strategic and sustained COVID-19 response may have played a critical role in mitigating adverse effects of the pandemic and point towards maturity, versatility and resilience of the HIV program in Kenya. Continued monitoring to assess long-term impact of the COVID-19 pandemic on HIV care and treatment program in Kenya is warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23294973v1" target="_blank">IMPACT OF THE COVID-19 PANDEMIC ON ROUTINE HIV CARE AND ANTIRETROVIRAL TREATMENT OUTCOMES IN KENYA: A NATIONALLY REPRESENTATIVE ANALYSIS</a>
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<li><strong>Individual and spatial determinants of mortality during the Covid-19 pandemic: The case of Belgium in 2020</strong> -
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Context. The year 2020 was marked by the Covid 19 pandemic. In Belgium, it led to a doubling in deaths, mainly grouped into two periods. This article aims to compare the relative importance of predictors and individual and spatial determinants of mortality during these two waves to an equivalent non-pandemic period and to identify whether and to what extent the pandemic has altered the sociodemographic patterns of conventional mortality. Methods. The analyses relate to all-cause mortality during the two waves of Covid-19 and their equivalent in 2019. They are based on matching individual and exhaustive data from the Belgian National Register with tax and population census data. A multi-level approach was adopted combining individual and spatial determinants. Results. Mortality patterns during the pandemic are very similar to those observed outside the pandemic. As in 2019, age, sex, and household composition significantly determine the individual risk of dying, with a higher risk of death among the oldest people, men, and residents of collective households. However, their risk of death increases during the Covid period, especially in the 65/79 age group. Spatial information is no more significant in 2020 than in 2019. However, a higher risk of death is observed when the local excess mortality index or the proportions of isolated or disadvantaged people increase. Conclusions. While the Covid pandemic did not fundamentally alter conventional mortality patterns, it did amplify some of the pre-existing differences in mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23295014v1" target="_blank">Individual and spatial determinants of mortality during the Covid-19 pandemic: The case of Belgium in 2020</a>
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<li><strong>Emerging Links Between COVID-19 and Cardiovascular & Cerebrovascular Thromboembolic Events: A Systematic Review</strong> -
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COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.05.23295067v1" target="_blank">Emerging Links Between COVID-19 and Cardiovascular &amp; Cerebrovascular Thromboembolic Events: A Systematic Review</a>
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<li><strong>Psychotherapies and Psychological Support for Individuals Facing Psychological Distress during the COVID-19 Pandemic: A Scoping Review</strong> -
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In this scoping review, we investigated psychotherapies and psychological support provided during the coronavirus disease 2019 (COVID-19) pandemic to clarify its recipients and the methods employed. We used Scopus and PubMed as the search engines on October 18, 2022, employing specific search terms (″COVID* ″ AND (″Psychotherap<em>″ OR ″psychological support</em>″) AND ″psychological distress*″). The initial search yielded 153 articles, of which 18 met the eligibility criteria after two rounds of screening. The distribution of participants ranged from the general population to patients with COVID-19 and those who had recovered. However, no studies of patients with post-COVID-19 sequelae were found. The distribution of the types of psychotherapies and psychological support varied and the use of new technology was suggested. Online interventions comprised the majority of the means of psychotherapies and psychological support. This study suggests that psychotherapies and psychological support during the COVID-19 pandemic were influenced by the social situation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.04.23295013v1" target="_blank">Psychotherapies and Psychological Support for Individuals Facing Psychological Distress during the COVID-19 Pandemic: A Scoping Review</a>
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<li><strong>Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study</strong> -
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Background. The overlapping clinical presentations of patients with acute respiratory disease can complicate disease diagnosis. Whilst PCR diagnostic methods to identify SARS-CoV-2 are highly sensitive, they have their shortcomings including false-positive risk and slow turnaround times. Changes in host gene expression can be used to distinguish between disease groups of interest, providing a viable alternative to infectious disease diagnosis. Methods. We interrogated the whole blood gene expression profiles of patients with COVID-19 (n=87), bacterial infections (n=88), viral infections (n=36), and not-infected controls (n=27) to identify a sparse diagnostic signature for distinguishing COVID-19 from other clinically similar infectious and non-infectious conditions. The sparse diagnostic signature underwent validation in a new cohort using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and then underwent further external validation in an independent in silico RNA-seq cohort. Findings. We identified a 10-gene signature (OASL, UBP1, IL1RN, ZNF684, ENTPD7, NFKBIE, CDKN1C, CD44, OTOF, MSR1) that distinguished COVID-19 from other infectious and non-infectious diseases with an AUC of 87.1% (95% CI: 82.6%-91.7%) in the discovery cohort and 88.7% and 93.6% when evaluated in the RT-qPCR validation, and in silico cohorts respectively. Interpretation. Using well-phenotyped samples collected from patients admitted acutely with a spectrum of infectious and non-infectious syndromes, we provide a detailed catalogue of blood gene expression at the time of hospital admission. The findings result in the identification of a 10-gene host diagnostic signature to accurately distinguish COVID-19 from other infection syndromes presenting to hospital. This could be developed into a rapid point-of-care diagnostic test, providing a valuable syndromic diagnostic tool for future early pandemic use.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.03.23294989v1" target="_blank">Differentiation of COVID-19 from other emergency infectious disease presentations using whole blood transcriptomics then rapid qPCR: a case-control and observational cohort study</a>
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<li><strong>Correlation of myeloid-derived suppressor cell expansion with upregulated transposable elements in severe COVID-19 unveiled in single-cell RNA sequencing reanalysis</strong> -
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Some studies investigated the potential role of transposable elements (TEs) in COVID-19 pathogenesis and complications. However, to the best of our knowledge, there is no study to examine the possible association of TEs expression in cell functions and its potential role in COVID-19 immune response at the single-cell level. In this study, we reanalyzed single-cell RNA seq data of bronchoalveolar lavage (BAL) samples obtained from six severe COVID-19 patients and three healthy donors to assess the probable correlation of TE expression with the immune responses induced by the SARS-CoV-2 virus in COVID-19 patients. Our findings indicated that the expansion of myeloid-derived suppressor cells (MDSCs (may be a characteristic feature of COVID-19. Additionally, a significant increase in TEs expression in MDSCs was observed. This upregulation of TEs in COVID-19 may be linked to the adaptability of these cells in response to their microenvironments. Furthermore, it appears that the identification of overexpressed TEs by Pattern recognition receptors (PRRs) in MDSCs may enhance the suppressive capacity of these cells. Thus, this study emphasizes the crucial role of TEs in the functionality of MDSCs during COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556192v1" target="_blank">Correlation of myeloid-derived suppressor cell expansion with upregulated transposable elements in severe COVID-19 unveiled in single-cell RNA sequencing reanalysis</a>
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<li><strong>Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.2.86</strong> -
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The continued evolution of SARS-CoV-2 may lead to evasion of vaccine immunity and natural immunity. A highly mutated Omicron variant BA.2.86 has recently been identified with over 30 amino acid changes in Spike compared with BA.2 and XBB.1.5. As of September 4, 2023, BA.2.86 has been identified in 37 sequences from 10 countries, which is likely an underestimate due to limited surveillance. The ability of BA.2.86 to evade NAbs compared with other currently circulating Omicron variants remains unknown. Our data show that NAb responses to BA.2.86 were lower than to BA.2 but were comparable or slightly higher than to the current circulating recombinant variants XBB.1.5, XBB.1.16, EG.5, EG.5.1, and FL.1.5.1.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556272v1" target="_blank">Neutralization Escape by SARS-CoV-2 Omicron Subvariant BA.2.86</a>
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<li><strong>Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</strong> -
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With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective immune responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 exhibited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), as well as the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 sera also showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 {degrees}C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.19.533338v2" target="_blank">Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</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 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>KAND567 Versus Placebo in Subjects Hospitalized With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: KAND567; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: Kancera AB<br/><b>Terminated</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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo<br/><b>Sponsor</b>: University of Chicago<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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19.</strong> - <b>Condition</b>: Nervous System Diseases<br/><b>Interventions</b>: Drug: Tianeptine; Drug: Placebo<br/><b>Sponsors</b>: Military Institute od Medicine National Research Institute; ABM Industries<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Pre-probiotic Supplementation for Post-covid Fatigue Syndrome</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo<br/><b>Sponsor</b>: University of Novi Sad, Faculty of Sport and Physical Education<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Primary exposure to SARS-CoV-2 via infection or vaccination determines mucosal antibody-dependent ACE2 binding inhibition</strong> - CONCLUSIONS: Our study provides new insights into the relationship between antibody isotypes and neutralization by using a sensitive and high-throughput ACE2 binding inhibition assay. Key differences are highlighted between vaccination and infection at the mucosal level, showing that despite differences in the quantity of the response, post-infection and post-vaccination ACE2 binding inhibition capacity did not differ.</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>Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study</strong> - CONCLUSIONS: In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.</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>Unleashing the link between the relaxation of the COVID-19 control policy and residents’ mental health in China: the mediating role of family tourism consumption</strong> - CONCLUSION: Based on the findings, the study proposes that government and policymakers should strengthen mental health intervention, improve access to mental health counseling, stimulate economic development, expand the employment of residents, and track the mutation of the novel coronavirus.</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>Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response</strong> - Phosgene is widely used as an industrial chemical, and phosgene inhalation causes acute lung injury (ALI), which may further progress into pulmonary edema. Currently, an antidote for phosgene poisoning is not known. Alpha-1 antitrypsin (α1-AT) is a protease inhibitor used to treat patients with emphysema who are deficient in α1-AT. Recent studies have revealed that α1-AT has both anti-inflammatory and anti-SARS-CoV-2 effects. Herein, we aimed to investigate the role of α1-AT in phosgene-induced…</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>RNA-dependent RNA polymerase of SARS-CoV-2 regulate host mRNA translation efficiency by hijacking eEF1A factors</strong> - The RNA-dependent RNA polymerase (NSP12) of COVID-19 plays a significant role in the viral infection process, which promotes viral RNA replication by cooperating with NSP7 and NSP8, but little is known about its regulation on the function of host cells. We firstly found that overexpression of NSP12 had little effect on host mRNAs transcription. Using iCLIP technology, we found that NSP12 can bind a series of host RNAs with the conserved binding motif G(C/A/G)(U/G/A)UAG, especially ribosomal RNA….</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>Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19</strong> - CONCLUSION: Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in 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>Betacoronaviruses SARS-CoV-2 and HCoV-OC43 Infections in IGROV-1 Cell Line Require Aryl Hydrocarbon Receptor</strong> - AbstractThe emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronaviruses SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course…</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>Radiologists’ experiences and perceptions regarding the use of teleradiology in South Africa</strong> - CONCLUSION: It is important to address structural barriers to the implementation of teleradiology. Clear communication strategies and multistakeholder engagement are also required.</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>Increased Fungal Infection Mortality Induced by Concurrent Viral Cellular Manipulations</strong> - Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A wild boar cathelicidin peptide derivative inhibits severe acute respiratory syndrome coronavirus-2 and its drifted variants</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress. However, the virus continues to mutate. Even when full vaccine coverage is achieved, vaccine-resistant mutants will likely emerge, thus requiring new annual vaccines…</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 the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation</strong> - SARS-CoV-2 induces major cellular lipid rearrangements, exploiting the host’s metabolic pathways to replicate. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that control lipid metabolism. SREBP1 is associated with the regulation of fatty acids, whereas SREBP2 controls cholesterol metabolism, and both isoforms are associated with lipid droplet (LD) biogenesis. Here, we evaluated the effect of SREBP in a SARS-CoV-2-infected lung epithelial cell line…</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>SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2</strong> - Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 10^(17) molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as…</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>High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells</strong> - The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication</strong> - Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple…</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>Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response</strong> - Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally,…</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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