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192 lines
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<title>26 October, 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>Changes in sleep duration during the long-lasting COVID-19 pandemic: individual and regional disparities</strong> -
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The adequate quality and quantity of sleep are related to maintaining the immune system and mental well-being; therefore, it is necessary to evaluate sleep duration during COVID-19. This study aimed to investigate the changes in sleep duration during the long-lasting COVID-19 period (2020 and 2021) in South Korea, and to examine the individual and regional disparities. The study population comprised 1,143,460 adults aged ≥19 years who participated in the 2017–2021 Korea Community Health Survey excluding those who did not respond to the daily sleep duration questionnaire. For statistical analysis, we first conducted a multiple regression model for 229 districts to estimate the district-specific changes in sleep duration. We then applied a meta-analysis to pool the 229 estimates and a meta-regression to examine the association between changes in sleep duration and regional characteristics. The sleep duration increased by 9.66 (95% CI: 8.53, 10.80) min in 2020 and 3.66 (95% CI: 2.09, 5.22) min in 2021 compared to the pre-pandemic period (2017–2019). The increase was more prominent in males, younger adults, employed individuals, and those with a high socioeconomic status compared to the general population. Communities with a higher proportion of apartments, lower normalized difference vegetation index in summer, and lower practice rate of moderate exercise were associated with a higher increase in sleep duration during the pandemic. The sleep duration increased during the COVID-19 pandemic, and the increase decreased as the COVID-19 lasted longer. The findings of our study highlight that preventive measures to manage sleep health during a pandemic should be framed in consideration of individual and regional characteristics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297531v1" target="_blank">Changes in sleep duration during the long-lasting COVID-19 pandemic: individual and regional disparities</a>
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</div></li>
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<li><strong>Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA</strong> -
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While SARS-CoV-2 vaccines have shown strong efficacy, their suboptimal uptake combined with the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no difference in disease severity between individuals infected with Delta and Omicron variants among the participants in this study, after controlling for other factors, and we found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within 270 days before infection was associated with decreased odds of moderate and severe outcomes, with the strongest association observed at 91-270 days post-vaccination. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297530v1" target="_blank">Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA</a>
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<li><strong>Fc-dependent functional activity of ChAdOx1-S and CoronaVac vaccine-induced antibodies to the SARS-CoV-2 spike protein</strong> -
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Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and COVID-19 disease severity is influenced by immunity acquired by natural exposure and/or vaccination, whereby most vaccines are formulated on the Ancestral strain. However, population-level immunity is complicated by the emergence of variants of concern (VOCs), such as Omicron that is the dominant variant currently in circulation. Antibody Fc-dependent effector functions are being increasingly recognised as important mediators in immunity, especially against VOCs. However, induction of these functions in populations with diverse infection and/or vaccination histories, remains poorly defined. Here, we evaluated Fc-dependent functional antibodies following vaccination with two widely used vaccines: AstraZeneca (AZ; ChAdOx1-S) and Sinovac (SV). We quantified FcγR-binding and C1q-fixing antibodies against Ancestral and variant spike (S) proteins in Brazilian adults vaccinated with AZ or SV (n=222), some of which were previously exposed to SARS-CoV-2. AZ induced greater FcγR-binding responses to Ancestral S than the SV vaccine. Previously exposed individuals had significantly greater vaccine-induced responses compared to their naïve counterparts, with notably high C1q-fixation levels, irrespective of vaccine type. FcγR-binding was highest among AZ vaccinated individuals with a prior exposure, and these responses were well retained against the Omicron S protein. Overall, these findings contribute to our understanding of vaccine-induced immunity and its effectiveness against evolving variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297503v1" target="_blank">Fc-dependent functional activity of ChAdOx1-S and CoronaVac vaccine-induced antibodies to the SARS-CoV-2 spike protein</a>
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<li><strong>Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection</strong> -
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BACKGROUND: Although RNA viruses like SARS-CoV-2 are generally thought to be transient, the persistence of viral components beyond the acute phase can be driven by a variety of virologic and immunologic factors. Recent studies have suggested that SARS-CoV-2 antigens may persist following COVID-19 but were limited by a lack of comparison to a large number of true negative control samples. METHODS: Using single molecule array (Simoa) assays for SARS-CoV-2 spike, S1, and nucleocapsid antigen in plasma from 171 pandemic-era individuals in the post-acute phase of SARS-CoV-2 infection and 250 pre-pandemic control samples, we compared prevalence of antigen detection. We used logistic regression models and prevalence ratios (PRs) to assess the relationship between demographic and disease factors and antigen persistence. RESULTS: Compared to the proportion of antigen positivity in the pre-pandemic controls (2%), detection of any SARS-CoV-2 antigen was more frequent across all post-acute COVID-19 time bins (3-6 months: 12.6%, p<0.001; 6-10 months, 10.7%, p=0.0002; 10-14 months, 7.5%, p=0.017). These differences were driven by spike protein for up to 14 months and nucleocapsid in the first 6 months after infection. The co-occurrence of multiple antigens at a single timepoint was uncommon. Hospitalization for acute COVID-19 (versus not hospitalized) and worse self-reported health during acute COVID-19 among those not hospitalized (versus more benign illness) were associated with higher prevalence of post-acute antigen detection (PR 1.86, p=0.03; PR 3.5, p=0.07, respectively) in the pandemic era. CONCLUSIONS: Our findings provide strong evidence that SARS-CoV-2 antigens can persist beyond the period of acute illness. The observation that more than 10% of plasma samples for over a year following initial SARS-CoV-2 infection contain detectable viral antigen, which are potentially immunogenic, has significant implications given the sheer number of people infected with SARS-CoV-2 to date. More work will be needed to determine whether these antigens have a causal role in post-acute sequelae of SARS-CoV-2 infection (PASC).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297114v1" target="_blank">Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection</a>
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<li><strong>Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 Vaccine</strong> -
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Background: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a Fall 2023 COVID-19 vaccine for adults 18 years and older on these outcomes. Methods: A previously developed Susceptible Exposed Infected Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19 related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. Results: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial vaccine effectiveness (VE) against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. Conclusions: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19 related infections, hospitalizations, and deaths.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297475v1" target="_blank">Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 Vaccine</a>
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<li><strong>Estimating the maximum risk of measles outbreaks due to heterogeneous fall in immunization rates</strong> -
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Immunization rates for childhoold vaccines, such as MMR, have seen a reduction over the recent years; this fall has only been accentuated after the COVID-19 pandemic. However, there is limited data on where the rates have reduced, and prior work has shown that heterogeneity in the drop in immunization rates has a significant impact on the risk of an outbreak. An important question from a public health perspective is: what is the maximum size of an outbreak in a region, when limited information is available on the fall in immunization rates within the region? This turns out to be a very hard computational problem. We develop a Bayesian optimization based approach for estimating the maximum outbreak size, and use it on a measles model for the state of Virginia. Our results show that the maximum outbreak size is several orders of magnitude higher than estimated in a baseline which assumes homogeneous fall. Even for a 5% reduction in the statewide immunzation rate, the expected outbreak size can be very high. The maximum outbreak size depends crucially on the importation location, i.e., where the disease starts, and importation in an urban region leads to a significantly higher outbreak. The outbreak size remains high even if the drop in immunization is bounded in health service areas in the state.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297486v1" target="_blank">Estimating the maximum risk of measles outbreaks due to heterogeneous fall in immunization rates</a>
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<li><strong>COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study</strong> -
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Background Information on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations. Methods Serum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18-59 vs 60-85 years) and medical risk conditions on GMC 2-6 weeks and 21-25 weeks after each vaccination, and on waning during 3-25 weeks after each vaccination, were estimated by linear regression. Results We included 20,816, 16,820 and 5,879 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2-6 and 21-25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2-6 weeks, higher GMC at 21-25 weeks, and slower waning. GMCs or waning after the first and second boosters (only 60-85) were not associated with medical risk conditions. Conclusions Since antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as disease severity rather than antibody levels are useful for prioritization of additional vaccinations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297192v1" target="_blank">COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study</a>
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<li><strong>Inferring community transmission of SARS-CoV-2 in the United Kingdom using the ONS COVID-19 Infection Survey</strong> -
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Key epidemiological parameters, including the effective reproduction number, R(t), and the instantaneous growth rate, r(t), generated from an ensemble of models, have been informing public health policy throughout the COVID-19 pandemic in the four nations of the United Kingdom of Great Britain and Northern Ireland (UK). However, estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the 9emergency9 to 9endemic9 phase of the pandemic. The Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) provided an opportunity to continue estimating these parameters in the absence of other data streams. We used a penalised spline model fitted to the ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over time. The resulting fitted curve was used to estimate the 9ONS-based9 R(t) and r(t) across the four nations of the UK. Estimates produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these parameters. Depending on the nation and parameter, we found that up to 77% of the variance in the government-published estimates can be explained by the ONS-based estimates, demonstrating the value of this singular data stream to track the epidemic in each of the four nations. We additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published estimates. Our work shows that the ONS CIS can be used to generate the key COVID-19 epidemics across the four UK nations. This is not intended as an alternative to ensemble modelling, rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297454v1" target="_blank">Inferring community transmission of SARS-CoV-2 in the United Kingdom using the ONS COVID-19 Infection Survey</a>
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<li><strong>Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Covalent Warhead</strong> -
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There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof towards human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLpro inhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = Paxlovid), CMX990 has distinctly differentiated potency (~5x more potent in primary cells) and human in vitro clearance (>4x better microsomal clearance and >10x better hepatocyte clearance), with good in vitro-in vivo correlation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.563688v1" target="_blank">Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Covalent Warhead</a>
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<li><strong>Cross-platform comparison of highly-sensitive immunoassays for inflammatory markers in a COVID-19 cohort</strong> -
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A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing antibody pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on serum samples from the NIH IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. Firstly, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Secondly, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Thirdly, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.563866v1" target="_blank">Cross-platform comparison of highly-sensitive immunoassays for inflammatory markers in a COVID-19 cohort</a>
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<li><strong>VIPERA: Viral Intra-Patient Evolution Reporting and Analysis</strong> -
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Viral mutations within patients nurture the adaptive potential of SARS-CoV-2 during chronic infections, which are a potential source of variants of concern. However, there is no integrated framework for the evolutionary analysis of intra-patient SARS-CoV-2 serial samples. Herein we describe VIPERA (Viral Intra-Patient Evolution Reporting and Analysis), a new software that integrates the evaluation of the intra-patient ancestry of SARS-CoV-2 sequences with the analysis of evolutionary trajectories of serial sequences from the same viral infection. It has been validated using positive and negative control datasets and successfully applied to a novel case, contributing to easy and automatic analysis of intra-patient SARS-CoV-2 sequences.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.561010v1" target="_blank">VIPERA: Viral Intra-Patient Evolution Reporting and Analysis</a>
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<li><strong>Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</strong> -
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The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, the usage of S2 as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design highly stable S2-only antigens retaining a closed prefusion conformation. Weighted ensemble simulations provide mechanistic characterization of the S2 trimer opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Alchemical free energy perturbation calculations and a corroborating set of experiments confirm that V991W and T998W in the central helices of S2 stabilize the trimer in the closed prefusion conformation, producing an antigen with increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.563841v1" target="_blank">Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</a>
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<li><strong>An infectious disease model with asymptomatic transmission and waning immunity</strong> -
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Infectious diseases present persistent challenges to global public health, demanding a comprehensive understanding of their dynamics to develop effective prevention and control strategies. The presence of asymptomatic carriers, individuals capable of transmitting pathogens without displaying symptoms, challenges conventional containment approaches focused on symptomatic cases. Waning immunity, the decline in protective response following natural recovery or vaccination, introduces further complexity to disease dynamics. In this paper, we developed a mathematical model to investigate the interplay between these factors, aiming to inform strategies for the management of infectious diseases. We derived the basic reproduction number for the model and showed that the disease would die out when this number falls below 1. We obtained a formula to estimate the relative contributions of asymptomatic and symptomatic transmission to the basic reproduction number, which remains unchanged when vaccination is included in the model. Through computer simulations with parameter values tailored for COVID-19 and sensitivity analysis, we demonstrated that population susceptibility significantly impacts the timing and magnitude of infection peaks. Populations with lower susceptibility experience delayed and less severe outbreaks. Vaccination was shown to play a crucial role in disease control, with an increased vaccination rate, extended immunity, and heightened vaccine efficacy proving pivotal. However, the effectiveness of these strategies hinges on maintaining a low vaccine escape proportion. Taken together, this study underscores the need for multifaceted, adaptable approaches to infectious disease management, highlighting the central role of vaccination in mitigating disease spread. Further research and validation with disease-specific data will enhance parameter estimates, improve model predictions, and inform evidence-based disease control strategies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.24.23297464v1" target="_blank">An infectious disease model with asymptomatic transmission and waning immunity</a>
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<li><strong>Evaluating aerosol and splatter during orthodontic debonding: implications for the COVID-19 pandemic</strong> -
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Introduction: Dental procedures often produce splatter and aerosol which have potential to spread pathogens such as SARS-CoV-2. Mixed guidance exists on the aerosol generating potential of orthodontic procedures. The aim of this study was to evaluate aerosol and/or splatter contamination during an orthodontic debonding procedure. Material and Methods: Fluorescein dye was introduced into the oral cavity of a mannequin. Orthodontic debonding was carried out in triplicate with filter papers placed in the immediate environment. Composite bonding cement was removed using a slow-speed handpiece with dental suction. A positive control condition included a high-speed air-turbine crown preparation. Samples were analysed using digital image analysis and spectrofluorometric analysis. Results: Contamination across the 8-metre experimental rig was 3% of the positive control on spectrofluorometric analysis and 0% on image analysis. There was contamination of the operator, assistant, and mannequin, representing 8%, 25%, and 28% of the positive control spectrofluorometric measurements, respectively. Discussion: Orthodontic debonding produces splatter within the immediate locality of the patient. Widespread aerosol generation was not observed. Conclusions: Orthodontic debonding procedures are low risk for aerosol generation, but localised splatter is likely. This highlights the importance of personal protective equipment for the operator, assistant, and patient.
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🖺 Full Text HTML: <a href="https://osf.io/djcus/" target="_blank">Evaluating aerosol and splatter during orthodontic debonding: implications for the COVID-19 pandemic</a>
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<li><strong>The Influence Of Covid-19 On Patient Mobilization And Injury Attributes In The ICU: A Retrospective Analysis Of A Level II Trauma Center</strong> -
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The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of traumatically-injured patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n=378) and after (n=499) April 1, 2020 when Georgia9s COVID-19 Shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student9s t-tests. A secondary analysis focused specifically on the after COVID patients examined the extent to which mobilization (n=328) or lack of mobilization (n=171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student9s -tests. The after COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before COVID patients. After COVID patients also had greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or day-to-mobilization. Within the after COVID cohort, those that were mobilized were older, a higher proportion were female, they had greater Glasgow Coma Scale scores, had longer total hospital days, and a lesser mortality rate. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297544v1" target="_blank">The Influence Of Covid-19 On Patient Mobilization And Injury Attributes In The ICU: A Retrospective Analysis Of A Level II Trauma Center</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>Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19; Coronavirus <br/><b>Interventions</b>: Device: eBAM Cov Testing <br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE <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>Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: EG-COVII <br/><b>Sponsors</b>: EyeGene 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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <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>Long COVID Brain Fog: Cognitive Rehabilitation Trial</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring <br/><b>Sponsors</b>: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Paradoxical Response to Chest Wall Loading in Mechanically Ventilated Patients</strong> - <b>Conditions</b>: ARDS; COVID-19; Mechanical Ventilation Pressure High; Ventilator-Induced Lung Injury <br/><b>Interventions</b>: Diagnostic Test: Manual loading of the chest wall <br/><b>Sponsors</b>: HealthPartners Institute <br/><b>Withdrawn</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 Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment <br/><b>Sponsors</b>: Chinese University of Hong Kong <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>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Inspiratory Muscle Training in People With Long COVID-19- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <br/><b>Active, not 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>Effects of Two Soluble ACE2-Fc Variants on Blood Pressure and Albuminuria in Hypertensive Mice: Research Letter</strong> - CONCLUSIONS: Soluble ACE2-Fc variant K reduces blood pressure and tends to lower albuminuria in hypertensive mice. Furthermore, soluble ACE2-Fc variant K has prolonged tissue retention, associated with increased tissue ACE2 activity. The results support further studies directed at the therapeutic potential of soluble ACE2-Fc variant K for cardiovascular and kidney protection.</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>Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections</strong> - Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades. Although several receptors and co-receptors have been reported for Ebola virus, key host factors remain to be elucidated. In this study, using a haploid cell screening platform, we identify the guanine nucleotide exchange factor CCZ1 as a key host factor in the early stage of filovirus replication. The critical role of CCZ1 for filovirus infections is validated in 3D…</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>TMPRSS2 is a functional receptor for human coronavirus HKU1</strong> - Four endemic seasonal human coronaviruses causing common colds, HKU1, 229E, NL63 and OC43 circulate worldwide¹. After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane-serine protease 2 (TMPRSS2) or endosomal cathepsins^(2-9). NL63 uses angiotensin-converting enzyme 2 (ACE2) as a receptor^(10), whereas 229E uses human aminopeptidase-N^(11). HKU1 and OC43 spikes bind cells through 9-O40 acelytated sialic acid but their protein receptors remain…</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>Epidemiological profile of COVID-19 in patients with prostate cancer undergoing androgen deprivation therapy at a Brazilian Cancer Center</strong> - CONCLUSION: Androgen deprivation therapy was not associated with protective factors or potential treatments in patients with prostate cancer and COVID-19. Although the number of patients analyzed was limited, and there may have been a selection bias, this is a unique study that cannot be expanded or replicated in similar (unvaccinated) populations.</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 lectin pathway of complement activation reduces Acute Respiratory Distress Syndrome severity in a mouse model of SARS-CoV-2 infection</strong> - Most COVID-19 patients requiring ICU care develop an acute respiratory distress syndrome (ARDS), characterised by severe hypoxemia, decreased lung compliance, and high vascular permeability. Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins reported in inflamed tissue and on the endothelium during COVID-19. Using a transgenic mouse model of SARS-CoV-2 infection we assessed the therapeutic utility of an inhibitory…</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>Computational screening of neuropilin 1 unveils novel potential anti-SARS-CoV-2 therapeutics</strong> - Neuropilin 1 (NRP-1) inhibition has shown promise in reducing the infectivity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and preventing the virus entry into nerve tissues, thereby mitigating neurological symptoms in COVID-19 patients. In this study, we employed virtual screening, including molecular docking, Molecular Dynamics (MD) simulation, and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations, to identify potential NRP-1 inhibitors. From a…</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 effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760</strong> - CONCLUSIONS: Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H(2)S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2…</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>Assessing the gene expression of the adenosine 5’-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients</strong> - CONCLUSION: Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation</strong> - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of “long COVID” neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y (MA30) , we demonstrated that intranasal inoculation of SARS2-N501Y (MA30) results 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>Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing</strong> - BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive…</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>Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis</strong> - OBJECTIVE: To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection.</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>ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS</strong> - Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show that ORF3c is expressed in SARS-CoV-2-infected cells and suppresses RIG-I- and MDA5-mediated IFN-β induction. ORF3c interacts with the signaling adaptor MAVS, induces its C-terminal cleavage, and inhibits the interaction…</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>Chemical Characteristics and Biological Activity Screening of Pistacia lentiscus Mastic Gum and Leaves from Turkiye</strong> - CONCLUSION: The mastic gum and leaves obtained from P. lentiscus may have great potential in terms of their chemical content, antiviral and cytotoxic activities. In ovo antiviral activity studies on the P. lentiscus were evaluated for the first time. Attributable to these properties, it is a sustainable, renewable natural resource that can be used as an additive and flavor in the food and pharmaceutical industries. This article is protected by copyright. All rights reserved.</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 Potential Peptide-Based Inhibitors against SARS-CoV-2 and Variants of Concern</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has greatly affected all aspect of life. Although several vaccines and pharmaceuticals have been developed against SARS-CoV-2, the emergence of mutated variants has raised several concerns. The angiotensin-converting enzyme (ACE2) receptor cell entry mechanism of this virus has not changed despite the vast mutation in emerging variants. Inhibiting the spike protein by which the virus identifies the host ACE2 receptor is a…</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>Some novel bioactivities of <em>Virgibacillus halodenitrificans</em> carotenoids, isolated from Wadi El-Natrun lakes</strong> - Carotenoids come in second among the most frequent natural pigments and are utilized in medications, nutraceuticals, cosmetics, food pigments, and feed supplements. Based on recent complementary work, Virgibacillus was announced for the first time as a member of Wadi El-Natrun salt and soda lakes microbiota, identified as Virgibacillus halodenitrificans, and named V. halodenitrificans DASH; hence, this work aimed to investigate several in vitro medicinal bioactivities of V. halodenitrificans…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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