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182 lines
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<title>27 May, 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>Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia</strong> -
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Objective The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in lower-income countries, we examine food insecurity during the pandemic period. Design Cross-sectional study using logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women. Setting The study is set in two communities in Eastern Ethiopia, one rural and one urban. Participants A random sample of 880 households residing in Kersa and Harar. Results Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income. Discussion After taking other characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings point to the need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23284545v3" target="_blank">Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia</a>
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<li><strong>What can New Zealand bats tell us about Coronaviruses?</strong> -
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The current Covid-19 pandemic emphasizes the dramatic consequences of emerging zoonotic pathogens and stimulates the need for an assessment of the evolution and natural cycle of such microbes in a One Health framework. A number of recent studies have revealed an astonishing diversity of bat-borne Coronaviruses, including in insular environments, which can be considered as simplified biological systems suited for the exploration of the transmission cycles of these viruses in nature. In this work, we present two new lineages of alpha Coronaviruses detected by screening the only two extant New Zealand bat species: the lesser short-tailed bat (Mystacina tuberculata) and the long-tailed bat (Chalinolobus tuberculatus). Infection prevalence reaching 60% in long-tailed bats makes this host-pathogen model relevant for the investigation of maintenance mechanisms in a bat reservoir with peculiar physiological adaptations to temperate climates. A phylogenetic analysis shows that these viral lineages do cluster with Coronaviruses hosted by bat sister species from Australia, supporting co-diversification processes and confirming that the evolution of these viruses is tightly linked to that of their hosts. These patterns provide an interesting framework for further research aiming at elucidating the natural history and biological cycles of these economically-devastating zoonotic viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.26.542035v1" target="_blank">What can New Zealand bats tell us about Coronaviruses?</a>
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<li><strong>Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors</strong> -
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The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. Additionally, in the lymphocyte compartment, CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.25.542297v1" target="_blank">Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors</a>
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<li><strong>Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes</strong> -
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RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and in silico sequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the IBV genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.25.542331v1" target="_blank">Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes</a>
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<li><strong>The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age</strong> -
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Given the profound effects of the COVID-19 pandemic on the way individuals interact, we sought to understand if there was an increase in pediatric first-time speech and language delay diagnoses in. We identified children under five years of age with a first-time speech delay diagnosis between January 1, 2018 and February 28, 2023, in Truveta Data. We calculated the monthly rate of first-time speech delay diagnoses per children with an encounter within the last year and no previous speech delay diagnosis. The Seasonal-Trend decomposition using LOESS (STL) method was used to adjust for seasonality. We also compared the difference in means between the 2018/2019 and 2021/2022 time periods. Significant increases in the mean of rates between 2018/2019 and 2021/2022 exist for the overall population and each age strata (p<0.001). Likely the causes of these trends are multifaceted and future research is needed to understand the specific drivers at play.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.18.23290122v1" target="_blank">The lasting effects of the pandemic: A time series analysis of first-time speech delays in kids under 5 years of age</a>
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<li><strong>The secretory IgA (sIgA) response in human milk against the SARS-CoV-2 Spike is highly durable and neutralizing for at least 1 year of lactation post-infection</strong> -
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Although in the early pandemic period, COVID-19 pathology among young children and infants was typically less severe compared to that observed among adults, this has not remained entirely consistent as SARS-CoV-2 variants have emerged. There is an enormous body of evidence demonstrating the benefits of human milk antibodies (Abs) in protecting infants against a wide range of enteric and respiratory infections. It is highly plausible that the same holds true for protection against SARS-CoV-2, as this virus infects cells of the gastrointestinal and respiratory mucosae. Understanding the durability of a human milk Ab response over time after infection is critical. Previously, we examined the Abs present in milk of those recently infected with SARS-CoV-2, and concluded that the response was secretory IgA (sIgA)-dominant and that these titers were highly correlated with neutralization potency. The present study aimed to monitor the durability of the SARS-CoV-2 IgA and secretory Ab (sAb) response in milk from COVID-19-recovered lactating individuals over 12 months, in the absence of vaccination or re-infection. This analysis revealed a robust and durable Spike-specific milk sIgA response, that at 9-12 months after infection, 88% of the samples exhibited titers above the positive cutoff for IgA and 94% were above cutoff for sAb. Fifty percent of participants exhibited less than a 2-fold reduction of Spike-specific IgA through 12 months. A strong significant positive correlation between IgA and sAb against Spike persisted throughout the study period. Nucleocapsid-specific Abs were also assessed, which revealed significant background or cross reactivity of milk IgA against this immunogen, as well as limited/inconsistent durability compared to Spike titers. These data suggests that lactating individuals are likely to continue producing Spike-specific Abs in their milk for 1 year or more, which may provide critical passive immunity to infants against SARS-CoV-2 throughout the lactation period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.19.23290192v1" target="_blank">The secretory IgA (sIgA) response in human milk against the SARS-CoV-2 Spike is highly durable and neutralizing for at least 1 year of lactation post-infection</a>
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<li><strong>Evaluation of the implementation and effects of management through care and services pathways: A protocol study</strong> -
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Background: In 2015, the Government of Quebec undertook a vast reorganization of its health and social services network. This reform mainly aimed to promote and simplify access to services for the population, contributing to the improvement of the quality and safety of care, and increasing the efficiency and effectiveness of the network. Since 2016, several health care organizations (HCOs) have pushed reform even further by developing management through care and service pathways (MCSP). This study aims to identify, in a processual manner, the different factors involved in implementing MCSP in different HCOs, in the turbulent context of the COVID-19 pandemic. Method: The methodology of this research project is based on developmental evaluation. The objective of developmental evaluation is to guide organizations and actors in the adaptation and development of innovations in complex and turbulent environments. Data will be collected over a three-year period using five strategies: i) organizational questionnaires; ii) analysis of clinical-administrative databases; iii) documentary analysis (grey and scientific literatures); iv) participant observations and v) semi-structured interviews with key actors involved in the implementation of MCSP. Discussion: In addition to the operationalization of pathways, the implementation of MCSP i) involves transforming the governance of the health care organization both at the strategic and operational levels and ii) is a demanding process that requires changes in practices, modifications in the allocation and configuration of resources and the development of new collaborations between the different actors in the organization, the partners and the users involved in this transformation. Several studies claim that governance innovations can create conditions that are favourable to the emergence of innovations in terms of available services and responding to the needs of populations. This research will develop knowledge of the factors involved in implementing MCSP in complex and turbulent contexts and propose scale-up across the province.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.25.23290549v1" target="_blank">Evaluation of the implementation and effects of management through care and services pathways: A protocol study</a>
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<li><strong>An Open One-Step RT-qPCR for SARS-CoV-2 detection</strong> -
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The COVID-19 pandemic has resulted in millions of deaths globally, and while several diagnostic systems were proposed, real-time reverse transcription polymerase chain reaction (RT-PCR) remains the gold standard. However, diagnostic reagents, including enzymes used in RT-PCR, are subject to centralized production models and intellectual property restrictions, which present a challenge for less developed countries. With the aim of generating a standardized One-Step open RT-qPCR protocol to detect SARS-CoV-2 RNA in clinical samples, we purified and tested recombinant enzymes and a non-proprietary buffer. The protocol utilized M-MLV RT and Taq DNA pol enzymes to perform a Taqman probe-based assay. Synthetic RNA samples were used to validate the One-Step RT-qPCR components, and the kit showed comparable sensitivity to approved commercial kits. The One-Step RT-qPCR was then tested on clinical samples and demonstrated similar performance to commercial kits in terms of positive and negative calls. This study represents a proof of concept for an open approach to developing diagnostic kits for viral infections and diseases, which could provide a cost-effective and accessible solution for less developed countries.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.29.21267000v2" target="_blank">An Open One-Step RT-qPCR for SARS-CoV-2 detection</a>
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<li><strong>The German Job Search Panel 2.0: The Pandemic Cohort</strong> -
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The German Job Search Panel (GJSP) comprises survey data from workers who registered as jobseekers expecting the termination of their jobs. The data include an exceptionally broad range of measures of health and well-being, among other information. A first cohort was invited to participate between November 2017 and May 2019 (Hetschko et al., 2022). In 2020, the outbreak of the Covid-19 pandemic drastically changed the macroeconomic environment of the German labor market and, in the process, the challenges associated with job search. We therefore decided to sample a second cohort of initially employed jobseekers from July 2020 to February 2021 (GJSP 2.0). Combining the two GJSP cohorts allows researchers to examine if and how the pandemic altered the experience of job search. This data report describes the pandemic cohort of the GJSP, changes to sampling, recruitment and questionnaires compared to the first cohort and documents determinants of participation and panel attrition.
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🖺 Full Text HTML: <a href="https://osf.io/szjrx/" target="_blank">The German Job Search Panel 2.0: The Pandemic Cohort</a>
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<li><strong>A Multi-Epitope/CXCL11 Prime/Pull Coronavirus Mucosal Vaccine Boosts the Frequency and the Function of Lung-Resident CD4+ and CD8+ Memory T Cells and Protects Against COVID-19-like Symptoms and Death Caused by SARS-CoV-2 infection</strong> -
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The pandemic of the coronavirus disease 2019 (COVID-19) has created the largest global health crisis in almost a century. Following exposure to SARS-CoV-2, the virus particles replicate in the lungs, induce a cytokine storm and potentially cause life-threatening inflammatory disease. Low frequencies of function SARS-CoV-2-specific CD4+ and CD8+ T cells in the lungs of COVID-19 patients were associated with severe cases of COVID-19. The apparent low level of T cell-attracting CXCL9, CXCL10, and CXCL11 chemokines in infected lungs may not be sufficient enough to assure the sequestration and/or homing of CD4+ and CD8+ T cells from the circulation into infected lungs. We hypothesize that a Coronavirus vaccine strategy that boosts the frequencies of functional SARS-CoV-2-specific CD4+ and CD8+ T cells in the lungs would lead to better protection against SARS-CoV-2 infection, COVID19-like symptoms, and death. In the present study, we designed and pre-clinically tested the safety, immunogenicity, and protective efficacy of a novel multi-epitope//CXCL11 prime/pull mucosal Coronavirus vaccine. This prime/pull vaccine strategy consists of intranasal delivery of a lung-tropic adeno-associated virus type 9 (AAV-9) vector that incorporates highly conserved human B, CD4+ CD8+ cell epitopes of SARS-CoV-2 (prime) and pulling the primed B and T cells into the lungs using the T cell attracting chemokine, CXCL-11 (pull). We demonstrated that immunization of HLA-DR<em>0101/HLA-A</em>0201/hACE2 triple transgenic mice with this multi-epitope//CXCL11 prime/pull Coronavirus mucosal vaccine: (i) Increased the frequencies of CD4+ and CD8+ TEM, TCM, and TRM cells in the lungs; and (ii) reduced COVID19-like symptoms, lowered virus replication, and prevented deaths following challenge with SARS-CoV-2. These findings discuss the importance of bolstering the number and function of lung-resident memory CD4+ and CD8+ T cells for better protection against SARS-CoV-2 infection, COVID-19-like symptoms, and death.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.23.542024v1" target="_blank">A Multi-Epitope/CXCL11 Prime/Pull Coronavirus Mucosal Vaccine Boosts the Frequency and the Function of Lung-Resident CD4+ and CD8+ Memory T Cells and Protects Against COVID-19-like Symptoms and Death Caused by SARS-CoV-2 infection</a>
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<li><strong>Modifications to the SR-Rich Region of the SARS-CoV-2 Nucleocapsid Regulate Self-Association and Attenuate RNA Interactions</strong> -
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The nucleocapsid protein (N) of SARS-CoV-2 is essential for virus replication, genome packaging, and maturation. N is comprised of two folded domains that are separated by a highly conserved, disordered, Ser/Arg-rich linker, and flanked by disordered tails. Using NMR spectroscopy and analytical ultracentrifugation we identify an alpha-helical region in the linker that undergoes concentration dependent self-association. NMR and gel shift assays show that the linker binds viral RNA but this binding is dampened by both phosphorylation and a naturally occurring mutation, whereas in contrast, RNA binding to the full-length protein is not affected. Interestingly, phase separation with RNA is significantly reduced upon phosphorylation but enhanced with the mutation. We attribute these differences to changes in the linker helix self-association which dissociates upon phosphorylation but forms more stable higher order oligomers in the variant. These data provide a structural mechanism for how the linker region contributes to protein-protein interactions, RNA-protein interactions, liquid-liquid phase separation and N protein regulation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.26.542392v1" target="_blank">Modifications to the SR-Rich Region of the SARS-CoV-2 Nucleocapsid Regulate Self-Association and Attenuate RNA Interactions</a>
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<li><strong>Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults</strong> -
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Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group - broad responders - neutralize a range of SARS-CoV-2 variants, whereas the other - narrow responders - neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.24.541920v1" target="_blank">Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults</a>
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<li><strong>Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load</strong> -
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Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes correlated with SARS-CoV-2 viral load over time were similarly differentially expressed across independent datasets of SARS-CoV-2 infected lung and upper airway cells, from both in vitro systems and patient samples. We also generated expression data on the human nose organoid model during SARS-CoV-2 infection. The human nose organoid-generated host transcriptional response captured many aspects of responses observed in the above patient samples while suggesting the existence of distinct host responses to SARS-CoV-2 depending on the cellular context, involving both epithelial and cellular immune responses. Our findings provide a catalog of SARS-CoV-2 host response genes changing over time.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.24.542181v1" target="_blank">Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load</a>
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<li><strong>Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation</strong> -
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Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and infection, we observed that pulmonary capillary endothelial cells (ECs) exhibit dramatic transcriptomic changes upon influenza injury punctuated by profound upregulation of Sparcl1. Endothelial deletion and overexpression of SPARCL1 implicated this secreted matricellular protein in driving key pathophysiologic symptoms of pneumonia, which we demonstrate result from its effects on macrophage polarization. SPARCL1 induces a shift to a pro-inflammatory "M1-like" phenotype (CD86+CD206-), thereby increasing associated cytokine levels. Mechanistically, SPARCL1 acts directly on macrophages in vitro to induce the pro-inflammatory phenotype via activation of TLR4, and TLR4 inhibition in vivo ameliorates inflammatory exacerbations caused by endothelial Sparcl1 overexpression. Finally, we confirmed significant elevation of SPARCL1 in COVID-19 lung ECs in comparison with those from healthy donors. Survival analysis demonstrated that patients with fatal COVID-19 had higher levels of circulating SPARCL1 protein compared to those who recovered, indicating the potential of SPARCL1 as a biomarker for prognosis of pneumonia and suggesting that personalized medicine approaches might be harnessed to block SPARCL1 and improve outcomes in high-expressing patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.25.541966v1" target="_blank">Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation</a>
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</div></li>
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<li><strong>The landscape of biomedical research</strong> -
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<div>
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The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D atlas of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We base our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we use a large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We use our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, and the distribution of gender imbalance in academic authorship. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.10.536208v2" target="_blank">The landscape of biomedical research</a>
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</div></li>
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</ul>
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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>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: green walking and intelligence gam<br/><b>Sponsors</b>: Bayburt University; Karadeniz Technical University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Special Discharge Training in the COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: COVID-19 Discharge Education<br/><b>Sponsor</b>: Kilis 7 Aralik University<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>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>: Patients With COVID-19<br/><b>Interventions</b>: Drug: The drug “Rutan 0.1”.; Other: Basic treatment<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19</strong> - <b>Conditions</b>: COVID-19 Vaccine; COVID-19<br/><b>Interventions</b>: Biological: 50 μg Baiya SARS-CoV-2 Vax 2; Other: Placebo<br/><b>Sponsor</b>: Baiya Phytopharm Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physiotherapy in Mutated COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Physiotherapy<br/><b>Sponsor</b>: Giresun University<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>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Rutan 25 mg; Other: Control group<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2373; Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant<br/><b>Sponsor</b>: Novavax<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>To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment.</strong> - <b>Conditions</b>: Fecal Microbiota Transplantation; COVID-19 Infection<br/><b>Intervention</b>: Procedure: Fecal microbiota transplantation<br/><b>Sponsor</b>: Shanghai 10th People’s Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona<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>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Baricitinib 4 MG<br/><b>Sponsors</b>: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale 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>Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: AZD3152; Other: Placebo<br/><b>Sponsor</b>: AstraZeneca<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-19 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccination Refusal<br/><b>Intervention</b>: Device: Patient Engagement tool<br/><b>Sponsors</b>: Queen Mary University of London; Social Action for Health<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>Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Other: Spray with Hypochlorous Acid Group; Other: Spray with Placebo Group<br/><b>Sponsor</b>: University of Monastir<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>Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug<br/><b>Sponsor</b>: Quratis Inc.<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>Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19)</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19<br/><b>Interventions</b>: Drug: AER002; Other: Placebo<br/><b>Sponsors</b>: Michael Peluso, MD; Aerium Therapeutics<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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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 and experimental validation of phthalocyanine and hypericin as effective SARS-CoV-2 fusion inhibitors</strong> - Phthalocyanine and hypericin have been previously identified as possible SARS-CoV-2 Spike glycoprotein fusion inhibitors through a virtual screening procedure. In this paper, atomistic simulations of metal-free phthalocyanines and atomistic and coarse-grained simulations of hypericins, placed around a complete model of the Spike embedded in a viral membrane, allowed to further explore their multi-target inhibitory potential, uncovering their binding to key protein functional regions and their…</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>Brain Reward Circuits Promote Stress Resilience and Health: Implications for Reward-Based Interventions</strong> - From the COVID-19 global pandemic to racial injustice and the continued impact of climate change on communities across the globe, the last couple of years have demonstrated the need for a greater understanding of how to protect people from the negative consequences of stress. Here, I outline a perspective on how the brain’s reward system might be an important, but often understudied, protective mechanism for stress resilience and stress-related health outcomes. I describe work suggesting that…</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>Optimizing the Cas13 antiviral train: cargo and delivery</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2020 highlighted the need for rapid, widespread responses against infectious disease. One such innovation uses CRISPR-Cas13 technology to directly target and cleave viral RNA, thereby inhibiting replication. Due to their programmability, Cas13-based antiviral therapies can be rapidly deployed to target emerging viruses, in comparison with traditional therapeutic development that takes at least 12-18 months, and often…</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>In silico design and evaluation of a novel therapeutic agent against the spike protein as a novel treatment strategy for COVID-19 treatment</strong> - CONCLUSIONS: In silico studies can provide a good opportunity to study viral proteins and new drugs or compounds since they do not need direct exposure to infectious agents or equipped laboratories. The suggested therapeutic agent should be further characterized in vitro and in vivo.</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>CD24-Siglec interactions in inflammatory diseases</strong> - CD24 is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with broad expression in multiple cell types. Due to differential glycosylation, cell surface CD24 have been shown to interact with various receptors to mediate multiple physiological functions. Nearly 15 years ago, CD24 was shown to interact with Siglec G/10 to selectively inhibit inflammatory response to tissue injuries. Subsequent studies demonstrate that sialylated CD24 (SialoCD24) is a major endogenous ligand for…</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 linear B-cell epitope close to the furin cleavage site within the S1 domain of SARS-CoV-2 Spike protein discriminates the humoral immune response of nucleic acid- and protein-based vaccine cohorts</strong> - CONCLUSIONS: Understanding the exact function of antibodies recognizing amino acid region 657-671 of SARS-CoV-2 Spike glycoprotein and why nucleic acid-based vaccines elicit different responses from protein-based ones will be helpful for future vaccine design.</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>Impacts of pregnancy and menopause on COVID-19 severity: A systematic review and meta-analysis of 4.6 million women</strong> - CONCLUSIONS: Pregnancy and menopause are protective and risk factors for severe COVID-19, respectively. The protective role of pregnancy on COVID-19 is minimal and could be counteracted or masked by prepregnancy or pregnancy comorbidities. The administration of estrogen and progesterone may prevent severe COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021)</strong> - The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was…</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 P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial</strong> - CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir</strong> - CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.</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>Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice</strong> - CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Promoting cognitive health: a virtual group intervention for community-living older adults</strong> - CONCLUSIONS: The synchronous virtual group intervention was shown to be feasible for the elderly in the community who participated in the study.</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 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19</strong> - The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant…</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>HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway</strong> - Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having 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>Evaluation of the Inhibition Potency of Nirmatrelvir against Main Protease Mutants of SARS-CoV-2 Variants</strong> - SARS-CoV-2 continues to pose a threat to public health. Main protease (M^(pro)) is one of the most lucrative drug targets for developing specific antivirals against SARS-CoV-2 infection. By targeting M^(pro), peptidomimetic nirmatrelvir is able to inhibit viral replication of SARS-CoV-2 and reduce the risk for progression to severe COVID-19. However, multiple mutations in the gene encoding M^(pro) of emerging SARS-CoV-2 variants raise a concern of drug resistance. In the present study, we…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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