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184 lines
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<title>23 April, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta infections</strong> -
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Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. Methods: Six national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. Results: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. Conclusions: All forms of natural and vaccine immunity prior to Omicron introduction provided strong protection against infection and severe COVID-19. Hybrid immunity conferred the strongest protection and its level was consistent with previous-infection immunity and vaccine immunity acting independently of each other.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.21.23288917v1" target="_blank">Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta infections</a>
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</div></li>
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<li><strong>A Proposed Process for Risk Mitigation During the COVID-19 Pandemic</strong> -
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Recent executive orders have led some Applied Behavior Analysis (ABA) providers to interpret themselves as “essential personnel” during the COVID-19 pandemic. In this article, we argue against a blanket interpretation that being labeled “essential personnel” means that all in person ABA services for all clients should continue during the COVID-19 pandemic. We believe this argument holds even if ABA providers are not in a jurisdiction currently under an active shelter at home or related order. First, we provide a brief description of risks associated with continued in person ABA service delivery as well as risks associated with the temporary suspension or transition to remote ABA service delivery. For many clients, continued in person service delivery carries a significant risk of severe harm to the client, their family and caregivers, the staff, and a currently overburdened healthcare system. In these situations, ABA providers should temporarily suspend services or transition to telehealth or other forms of remote service delivery until information from federal, state, and local healthcare experts deem in person contact safe. In rare cases, temporary suspension or transition to remote service delivery may place the client or others at risk of significant harm. In these situations in person services should likely continue and ongoing assessment and risk mitigation are essential.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/buetn/" target="_blank">A Proposed Process for Risk Mitigation During the COVID-19 Pandemic</a>
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<li><strong>An in vitro experimental pipeline to characterize the binding specificity of SARS-CoV-2 neutralizing antibodies</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to over 760 million cases and >6.8 million deaths worldwide. We developed a panel of human neutralizing monoclonal antibodies (mAbs) targeting the SARS-CoV-2 Spike protein using Harbour H2L2 transgenic mice immunized with Spike receptor binding domain (RBD) (1). Representative antibodies from genetically-distinct families were evaluated for inhibition of replication-competent VSV expressing SARS-CoV-2 Spike (rcVSV-S) in place of VSV-G. One mAb (denoted FG-10A3) inhibited infection of all rcVSV-S variants; its therapeutically-modified version, STI-9167, inhibited infection of all tested SARS-CoV-2 variants, including Omicron BA.1 and BA.2, and limited virus proliferation in vivo (1). To characterize the binding specificity and epitope of FG-10A3, we generated mAb-resistant rcVSV-S virions and performed structural analysis of the antibody/antigen complex using cryo-EM. FG-10A3/STI-9167 is a Class 1 antibody that prevents Spike-ACE2 binding by engaging a region within the Spike receptor binding motif (RBM). Sequencing of mAb-resistant rcVSV-S virions identified F486 as a critical residue for mAb neutralization, with structural analysis revealing that both the variable heavy and light chains of STI-9167 bound the disulfide-stabilized 470-490 loop at the Spike RBD tip. Interestingly, substitutions at position 486 were later observed in emerging variants of concern BA.2.75.2 and XBB. This work provides a predictive modeling strategy to define the neutralizing capacity and limitations of mAb therapeutics against emerging SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.20.537738v1" target="_blank">An in vitro experimental pipeline to characterize the binding specificity of SARS-CoV-2 neutralizing antibodies</a>
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</div></li>
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<li><strong>Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making</strong> -
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Background: The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Methods: Using archived forecasts from the California Department of Public Health9s California COVID Assessment Tool (https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Results: Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Conclusions: Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.08.22282086v2" target="_blank">Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making</a>
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<li><strong>Evaluation of coronavirus decay in French coastal water and application to SARS-CoV-2 risk evaluation using Porcine Epidemic Diarrhea Virus as surrogate.</strong> -
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SARS-CoV-2 in infected patient mainly display pulmonary and oronasal tropism however, the presence of the virus has also been demonstrated in stools of patients and consequently in wastewater treatment plant effluents, questioning the potential risk of environmental contamination (such as seawater contamination) through inadequately treated wastewater spill-over into surface or coastal waters. The environmental detection of RNA alone does not substantiate risk of infection, and evidence of an effective transmission is not clear where empirical observations are lacking. Therefore, here, we decided to experimentally evaluate the persistence and infectious capacity of the Porcine epidemic diarrhea virus (PEDv), considered as a coronavirus representative model and SARS-CoV-2 surrogate, in the coastal environment of France. Coastal seawater was collected, sterile-filtered, and inoculated with PEDv before incubation for 0–4 weeks at four temperatures representative of those measured along the French coasts throughout the year (4, 8, 15, and 24°C). The decay rate of PEDv was determined using mathematical modeling and was then used to determine the half-life of the virus along the French coast in accordance with temperatures from 2000 to 2021. We experimentally observed an inverse correlation between seawater temperature and the persistence of infectious viruses in seawater and confirm that the risk of transmission of infectious viruses from contaminated stool in wastewater to seawater during recreational practices is very limited. The present work represents a good model to assess the risk of transmission of not only SARS-CoV-2 but may also be used to model the risk of other coronaviruses, specifically enteric coronaviruses.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.18.23288060v1" target="_blank">Evaluation of coronavirus decay in French coastal water and application to SARS-CoV-2 risk evaluation using Porcine Epidemic Diarrhea Virus as surrogate.</a>
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</div></li>
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<li><strong>Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19</strong> -
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Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18- hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.09.17.460664v3" target="_blank">Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation in type I interferon and cytokine responses in COVID-19</a>
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</div></li>
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<li><strong>Optimality of Maximal-Effort Vaccination</strong> -
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It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.12.22275015v3" target="_blank">Optimality of Maximal-Effort Vaccination</a>
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<li><strong>Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity</strong> -
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Human coronaviruses (HCoVs) cause respiratory tract infections and are of great importance due to the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Human betacoronavirus OC43 (HCoV-OC43) is an adequate surrogate for SARS-CoV-2 because it infects the human respiratory system, presents a comparable biology, and is transmitted in a similar way. Its use is advantageous since it only requires biosafety level (BSL)-2 infrastructure which minimizes costs and biosafety associated limitations. In this report, we describe a high-throughput screening (HTS) platform to identify compounds that inhibit the propagation of HCoV-OC43. Optimization of assays based on inhibition of the cytopathic effect and virus immunodetection with a specific antibody, has provided a robust methodology for the screening of a selection of microbial natural product extracts from the Fundacion MEDINA collection. Using this approach, a subset of 1280 extracts has been explored. Of these, upon hit confirmation and early LC-MS dereplication, 10 extracts were identified that contain potential new compounds. In addition, we report on the novel antiviral activity of some previously described natural products whose presence in bioactive extracts was confirmed by LC/MS analysis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.20.537680v1" target="_blank">Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity</a>
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<li><strong>Overburdened Bureaucrats: Providing Equal Access to Public Services during COVID-19</strong> -
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Discriminatory treatment of minorities by bureaucrats remains a serious challenge. A dominant explanation argues that bureaucrats discriminate because of high workloads in public organizations, but few empirical studies test this outside of the lab. In this study, I investigate whether workload matters for discrimination in a real-world public service context during the COVID-19 pandemic in Denmark in 2020. I document that unemployment services experienced a substantial increase in workload due to a 20% rise in unemployment and exploit the fact that the increase happened suddenly and spread asymmetrically. I use micro-level register data on bureaucrat-client interactions on more than 380,000 unemployed and examine whether bureaucrats provided fewer services to citizens of non-Western descent. The finding reveals that the substantial workload associated with the COVID-19 pandemic did not lead to increased discrimination. I discuss the special circumstances associated with the COVID-19 pandemic and the possible role of organizational structure and professional norms.
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🖺 Full Text HTML: <a href="https://osf.io/zmt5y/" target="_blank">Overburdened Bureaucrats: Providing Equal Access to Public Services during COVID-19</a>
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<li><strong>Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science</strong> -
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Biopsy is crucial in clinical medicine to obtain tissues and cells that may directly reflect the pathological changes of each disease. However, the brain is an exception due to ethical and practical challenges. Nasal biopsy, which captures olfactory neurons and their progenitors, has been considered as an alternative method of obtaining neuronal cells from living patients. Multiple groups, including us, have enriched olfactory neuronal cells (ONCs) from nasal biopsied tissue. ONCs can be obtained from repeated biopsies in a longitudinal study, providing mechanistic insight associated with dynamic changes along the disease trajectory and treatment response. Nevertheless, molecular characterization of nasal biopsied cells/tissue has been insufficient. Taking advantage of recent advances in next-generation sequencing technologies at the single-cell resolution and related rich public databases, we aimed to define the neuronal characteristics of ONCs, their homogeneity, and their utility. We conducted single-cell and bulk RNA sequencing, analyzed and compared the data with multiple public datasets. We observed that the molecular signatures of ONCs are similar to those of neurons, distinct from major glial cells. The signatures of ONCs resemble those of developing neurons and share features of excitatory neurons in the prefrontal and cingulate cortex. The high homogeneity of ONCs is advantageous in pharmacological, functional, and protein studies. Together, the present data solidify the utility of ONCs in studying molecular mechanisms and exploring objective biomarkers for brain disorders. The ONCs may also be useful in studying the potential link between the olfactory epithelium impairment and the resultant mental dysfunction elicited by SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.23.509290v2" target="_blank">Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science</a>
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<li><strong>Machine learning detection of SARS-CoV-2 high-risk variants</strong> -
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved many high-risk variants, resulting in repeated COVID-19 waves of pandemic during the past years. Therefore, accurate early-warning of high-risk variants is vital for epidemic prevention and control. Here we construct a machine learning model to predict high-risk variants of SARS-CoV-2 by LightGBM algorithm based on several important haplotype network features. As demonstrated on a series of different retrospective testing datasets, our model achieves accurate prediction of all variants of concern (VOC) and most variants of interest (AUC=0.96). Prediction based on the latest sequences shows that the newly emerging lineage BA.5 has the highest risk score and spreads rapidly to become a major epidemic lineage in multiple countries, suggesting that BA.5 bears great potential to be a VOC. In sum, our machine learning model is capable to early predict high-risk variants soon after their emergence, thus greatly improving public health preparedness against the evolving virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.19.537460v1" target="_blank">Machine learning detection of SARS-CoV-2 high-risk variants</a>
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<li><strong>Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses</strong> -
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The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learned. As a component of the Platform, the SARS-CoV-2 Data Hubs enabled the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.19.537514v1" target="_blank">Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses</a>
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<li><strong>SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replication in vitro</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is believed to have a zoonotic origin. Bats are a suspected natural host of SARS-CoV-2 because of sequence homology with other bat coronaviruses. Understanding the origin of the virus and determining species susceptibility is essential for managing the transmission potential during a pandemic. In a previous study, we established an in vitro animal model of SARS-CoV-2 susceptibility and replication in a non-permissive avian fibroblast cell line (DF1) based on expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) from different animal species. In this work, we express the ACE2 of seven bat species in DF1 cells and determine their ability to support attachment and replication of the original SARS-CoV-2 Wuhan lineage virus, as well as two variants, Delta and Lambda. We demonstrate that the ACE2 receptor of all seven species: little brown bat (Myotis lucifugus), great roundleaf bat (Hipposideros armiger), Pearson’s horseshoe bat (Rhinolophus pearsonii), greater horseshoe bat (Rhinolophus ferrumequinum), Brazilian free-tailed bat (Tadarida brasiliensis), Egyptian rousette (Rousettus aegyptiacus), and Chinese rufous horseshoe bat (Rhinolophus sinicus), made the DF1 cells permissible to the three isolates of SARS-CoV-2. However, the level of virus replication differed between bat species and variant tested. In addition, the Wuhan lineage SARS-CoV-2 virus replicated to higher titers (104.5 -105.5 TCID50) than either variant virus (103.5-104.5 TCID50) on pass 1. Interestingly, all viruses tested grew to higher titers (approximately 106 TCID50) when cells expressed the human ACE2 gene compared to bat ACE2. This study provides a practical in vitro method for further testing of animal species for potential susceptibility to current and emerging SARS-CoV-2 viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.19.537521v1" target="_blank">SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replication in vitro</a>
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<li><strong>A rapid review of the effectiveness, efficiency, and acceptability of surgical hubs in supporting planned care activity</strong> -
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The COVID-19 pandemic further exacerbated disruptions to elective care services in the UK, leading to longer waits for treatment and a growing elective surgery backlog. There have been growing calls for the creation of surgical hubs to help reduce this backlog. Surgical hubs aim to increase surgical capacity by providing quicker access to procedures, as well as facilitate infection control by segregating patients and staff from emergency care. This rapid review aimed to assess the effectiveness, efficiency, and acceptability of surgical hubs in supporting planned care activity, to inform the implementation of these hubs in Wales. The review identified evidence available up until January 2023. Twelve primary studies were included, eight of which used comparative methods. Most of the studies were conducted during the COVID-19 pandemic and described surgical hubs designed mainly to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Outcome measures reported included clinical, performance, economic, and patient reported outcomes across a variety of different surgical disciplines. Most of the studies did not describe surgical hubs based on their structure, i.e., standalone, integrated, or ring-fenced hubs. The evidence relating to the impact of surgical hubs on clinical outcomes appeared to be heterogenous and limited. Included studies did not appear to control for the impact of the COVID-19 pandemic on outcomes. Evidence of the impact of surgical hubs on performance outcomes such as efficiency, utilisation/usage, volume of surgeries/treatments, performance, cancellations, and time from diagnosis to treatment is limited. Evidence relating to the economic impact of surgical hubs is also limited, however there is evidence to suggest that total average costs are lower in surgical hubs when compared to general hospitals. Evidence relating to the impact of surgical hubs on patient reported outcomes is limited but indicates there may be a positive effect on patient satisfaction and compliance. Considerable variation in the types of surgical hubs reviewed, surgical disciplines, along with the small number of comparative studies, as well as methodological limitations across included studies, could limit the applicability of these findings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.20.23288815v1" target="_blank">A rapid review of the effectiveness, efficiency, and acceptability of surgical hubs in supporting planned care activity</a>
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<li><strong>Mortality among persons with HIV in the United States during the COVID-19 pandemic: a population-level analysis</strong> -
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Background: Whether COVID-19 has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how COVID-19 and subsequent behavioral changes affected mortality among PWDH. Methods: We obtained mortality and population size data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the PWDH population aged ≥13 years in the United States, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex-at birth were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. Results: Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. The mortality risk ratio between PWDH and the general population decreased 7.7% in 2020. Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH above 55 and older representing the majority of excess deaths. Conclusions: While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller than those observed in the general population. This suggests that COVID-19 and resulting behavioral changes among PWDH did not result in disproportionate mortality among PWDH. These findings suggest that COVID-19, and any associated indirect effects, do not represent a proportionally greater risk for PWDH compared to the general population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.19.23288817v1" target="_blank">Mortality among persons with HIV in the United States during the COVID-19 pandemic: a population-level analysis</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>Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Standard of Care + Quinine Sulfate; Drug: Standard of Care<br/><b>Sponsors</b>: Universitas Padjadjaran; National Research and Innovation Agency of Indonesia; Prodia Diacro Laboratories P.T.<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>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Biological: MSC-derived exosomes<br/><b>Sponsors</b>: Huazhong University of Science and Technology; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>: Omicron Variant of COVID-19<br/><b>Intervention</b>: Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>: Xiangao Jiang<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-1283.222; Biological: mRNA-1273.222<br/><b>Sponsor</b>: ModernaTX, Inc.<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>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: RD-X19; Device: Sham<br/><b>Sponsor</b>: EmitBio Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ropeginterferon alfa-2b; Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University 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>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation<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>Postoperative Sugammadex After COVID-19</strong> - <b>Conditions</b>: General Anesthesia; COVID-19<br/><b>Interventions</b>: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg<br/><b>Sponsor</b>: Korea University Ansan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azeliragon; Drug: Placebo<br/><b>Sponsor</b>: Salim S. Hayek<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>Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)<br/><b>Sponsor</b>: Azienda Socio Sanitaria Territoriale di Lecco<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination</strong> - <b>Conditions</b>: Vaccine Refusal; COVID-19<br/><b>Interventions</b>: Behavioral: Informational Video; Behavioral: Altruistic Video; Behavioral: Individualistic Video<br/><b>Sponsor</b>: Sir Mortimer B. Davis - Jewish 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>Effect of Telerehabilitation Practice in Long COVID-19 Patients</strong> - <b>Conditions</b>: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care<br/><b>Sponsor</b>: Indonesia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rehabilitation Treatment of Patients With COVID-19</strong> - <b>Conditions</b>: Rehabilitation; Pneumonia, Viral; COVID-19; Quality of Life<br/><b>Interventions</b>: Other: exercises; Other: massage<br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University; MEDSI Clinical Hospital 1, ICU<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral activities of hemp cannabinoids</strong> - Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids. After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human…</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>Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds</strong> - The study aimed to prospect in silico native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti-SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of…</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>Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19</strong> - Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary…</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>Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with Granulomatosis with polyangiitis</strong> - CONCLUSIONS: Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.</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>Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration</strong> - CONCLUSIONS: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.</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>MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8</strong> - CONCLUSIONS: Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.</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>Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase</strong> - Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2’-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2’-O-RNA MTase…</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 of SARS-CoV-2 M<sup>pro</sup> inhibitors bearing a cinnamic ester warhead with <em>in vitro</em> activity against human coronaviruses</strong> - COVID-19 now ranks among the most devastating global pandemics in history. The causative virus, SARS-CoV-2, is a new human coronavirus (hCoV) that spreads among humans and animals. Great efforts have been made to develop therapeutic agents to treat COVID-19, and among the available viral molecular targets, the cysteine protease SARS-CoV-2 M^(pro) is considered the most appealing one due to its essential role in viral replication. However, the inhibition of M^(pro) activity is an interesting…</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>Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function</strong> - Acute lung injury (ALI) is an acute and devastating disease caused by systemic inflammation e.g. patients infected with bacteria and viruses such as SARS-CoV-2 have an unacceptably high mortality rate. It has been well documented that endothelial cell damage and repair play a central role in the pathogenesis of ALI because of its barrier function. Nevertheless, the leading compounds that effectively accelerate endothelial cell repair and improve barrier dysfunction in ALI are largely unknown. 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>Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis</strong> - Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HRESIMS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3’-C-8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak…</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>Integrin β1 is a key determinant of the expression of angiotensin-converting enzyme 2 (ACE2) in the kidney epithelial cells</strong> - The expression of the angiotensin-converting enzyme 2 (ACE2) is altered in multiple chronic kidney diseases like hypertension and renal fibrosis, where the signaling from the basal membrane proteins is critical for the development and progression of the various pathologies. Integrins are heterodimeric cell surface receptors that have important roles in the progression of these chronic kidney diseases by altering various cell signaling pathways in response to changes in the basement membrane…</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>Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results</strong> - CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.</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>Awareness raising and dealing with methanol poisoning based on effective strategies</strong> - Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are…</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>Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease</strong> - The 3-chymotrypsin-like protease 3CLpro from SARS-CoV-2 is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using a HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by 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>Transcription factor <em>Dmrt1</em> triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility</strong> - Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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