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<title>07 March, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Care-full Collectives and their Care Practices</strong> -
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In my dissertation, I examine different collectives and their practices through different applied theories of care and theorize on new organizational structures and rituals. This is a study of how people came together during the first wave of Covid-19, myself included. It studies these coming-togethers through different “do-ings” and “be–ings” and juxtaposes them with different theories of care. Theories that include Annemarie Mol’s “Logic of Care”, Ella Myers’ “Worldly things”, Jenna Grant’s “Repair as Care”, Sara Ahmed’s “Fragile Connections” and Lucy Suchman’s “Relocating Innovation”. These different theories come from places like medical anthropology, STS, queer theory, and more. I give an honest account of my journey through these collectives and these theories. I also start to propose an alternate way of organizing institutions for mutual aid through two tools - archetypes and axioms.
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🖺 Full Text HTML: <a href="https://osf.io/ds39u/" target="_blank">Care-full Collectives and their Care Practices</a>
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</div></li>
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<li><strong>Providing the Ichushi-Web Bibliographies to WHO COVID-19 Research Database: Corona-related information service during pandemic disasters.</strong> -
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Three years after we began living through an unprecedented infectious disease epidemic at the end of 2019, our world is still heavily affected by the novel coronavirus. Compared to the beginning of the epidemic, when there was no information at all, researchers and health care workers around the world have been sharing information and examining the characteristics of this virus and infection prevention and treatment measures in order to respond to this situation. Preprints are also being used as the fastest route for information distribution, and research information on novel coronaviruses, in particular, is circulating at an explosive volume and speed. New tools such as the LitCovid, the iSearch COVID-19 portfolio, and the WHO COVID-19 Research Database(WHO COVID-19 RDB), which collect and provide information specific to novel coronavirus infection, have also appeared. This article introduces the activities of providing the Ichushi-Web bibliographies to the WHO COVID-19 RDB and what I realized from these experiences, as well as an overview of this database.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/7gsxr/" target="_blank">Providing the Ichushi-Web Bibliographies to WHO COVID-19 Research Database: Corona-related information service during pandemic disasters.</a>
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</div></li>
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<li><strong>Prediction of SARS-CoV-2 transmission dynamics based on population-level cycle threshold values: A Machine learning and mechanistic modeling study</strong> -
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Background: Polymerase chain reaction (PCR) cycle threshold (Ct) values can be used to estimate the viral burden of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) and predict population-level epidemic trends. We investigated the use of machine learning (ML) and epidemic transmission modeling based on Ct value distribution for SARS-CoV-2 incidence prediction during an Omicron-predominant period.
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</p>
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Methods: Using simulated data, we developed a ML model to predict the reproductive number based on Ct value distribution, and validated it on out-of-sample province-level data. We also developed an epidemiological model and fitted it to province-level data to accurately predict incidence.
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</p>
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Results: Based on simulated data, the ML model predicted the reproductive number with highest performance on out-of-sample province-level data. The epidemiological model was validated on outbreak data, and fitted to province-level data, and accurately predicted incidence.
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</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Conclusions: These modeling approaches can complement traditional surveillance, especially when diagnostic testing practices change over time. The models can be tailored to different epidemiological settings and used in real time to guide public health interventions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.06.23286837v1" target="_blank">Prediction of SARS-CoV-2 transmission dynamics based on population-level cycle threshold values: A Machine learning and mechanistic modeling study</a>
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</div></li>
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<li><strong>Modeling Biases in SARS-CoV-2 infections Prediction using Genome Copies Concentration in Wastewater</strong> -
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Background: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, can be detected in stool samples and subsequently shed in the sewage system. The field of Wastewater-based epidemiology (WBE) aims to use this valuable source of data for epidemiological surveillance, as it has the potential to identify unreported infections and to anticipate the need for diagnostic tests. Objectives: The objectives of this study were to analyze the absolute concentration of genome copies of SARS-CoV-2 shed in Catalonia9s wastewater during the Omicron peak in January 2022, and to develop a mathematical model capable of using wastewater data to estimate the actual number of infections and the temporal relationship between reported and unreported infections. Methods: We collected twenty-four-hour composite 1-liter samples of wastewater from 16 wastewater treatment plants (WWTPs) in Catalonia on a weekly basis. We incorporated this data into a compartmental epidemiological model that distinguishes between reported and unreported infections and uses a convolution process to estimate the genome copies shed in sewage. Results: The 16 WWTPs showed an average correlation of 0.88 ± 0.08 (ranging from 0.96 to 0.71) and an average delay of 8.7 ± 5.4 days (ranging from 0 to 20 days). Our model estimates that about 53% of the population in our study had been infected during the period under investigation, compared to the 19% of cases that were detected. This under-reporting was especially high between November and December 2021, with values up to 10. Our model also allowed us to estimate the maximum quantity of genome copies shed in a gram of feces by an infected individual, which ranged from 4.15 × 10^7 gc/g to 1.33 × 10^8 gc/g. Discussion: Although wastewater data can be affected by uncertainties and may be subject to fluctuations, it can provide useful insights into the current trend of an epidemic. As a complementary tool, WBE can help account for unreported infections and anticipate the need for diagnostic tests, particularly when testing rates are affected by human behavior-related biases.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.06.23286832v1" target="_blank">Modeling Biases in SARS-CoV-2 infections Prediction using Genome Copies Concentration in Wastewater</a>
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</div></li>
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<li><strong>The single item burnout measure is a reliable and valid tool to measure occupational burnout</strong> -
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OBJECTIVE To estimate the reliability and the validity of the single item burnout measure in a sample of nurses in Greece. METHOD We conducted an online cross-sectional study in Greece with 963 nurses. Data were collected during October 2022. We measured demographic and work-related variables of nurses, i.e. gender, age, chronic disease, self-rated health status, years of experience, and working in COVID-19 ward/intensive care unit. We used the single item burnout (SIB) and the Copenhagen Burnout Inventory (CBI) to measure occupational burnout. Moreover, we used the COVID-19 burnout scale (COVID-19-BS) to measure nurses burnout during the pandemic, and the Patient Health Questionnaire-4 (PHQ-4) to measure anxiety and depression among nurses. RESULTS Intraclass correlation coefficient between the two measurements of the SIB during the test-retest study was 0.986 indicating excellent reliability of the SIB. We found a high correlation between CBI factors and SIB (p<0.001), a moderate correlation between PHQ-4 and SIB (p<0.001), and a low to moderate correlation between COVID-19-BS and SIB (p<0.001). Therefore, concurrent validity of SIB was excellent. Moreover, SIB had high discriminant validity. In particular, nurses with a chronic disease, those with a very poor/poor/moderate health status, and those working in COVID-19 ward/intensive care unit had higher levels of burnout according to the SIB (p<0.001 in all cases). Moreover, we found a positive relationship between years of experience and SIB score (r=0.13, p<0.001). CONCLUSIONS The single item burnout measure is a brief, reliable, and valid tool that we can use as a screening measure to identify individuals at high risk of burnout.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.06.23286842v1" target="_blank">The single item burnout measure is a reliable and valid tool to measure occupational burnout</a>
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</div></li>
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<li><strong>Viral kinetics of sequential SARS-CoV-2 infections</strong> -
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The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we compared the SARS-CoV-2 viral kinetics of first vs. second infections, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a lower peak viral concentration and faster clearance time, especially in individuals who received a vaccine dose between their first and second infection. Furthermore, a person9s relative (rank-order) viral clearance time, compared to others infected with the same variant, was similar across first and second infections; that is, individuals who had a relatively fast clearance time in their first infection tended to also have a relatively fast clearance time in their second infection. These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person9s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.03.23286775v1" target="_blank">Viral kinetics of sequential SARS-CoV-2 infections</a>
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</div></li>
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<li><strong>Cooperative and structural relationships of the trimeric Spike with infectivity and antibody escape of the strains Delta (B.1.617.2) and Omicron (BA.2, BA.5, and BQ.1)</strong> -
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<div>
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Herein, we simulated the trimeric Spike of the variants B.1.617.2, BA.2, BA.5 and BQ.1 for 300 ns. We derived mechanisms by which the substitutions K417N, L452R, N444T and N460K may favor resistance to neutralizing antibodies. The K417N and L452R contribute to the expansion of the networks of hydrogen bonding interactions with neighboring residues, decreasing their capacity to interact with neutralizing antibodies. The SpikeBQ.1 possesses two unique K444T and N460K mutations that expand the network of hydrogen bonding interactions. This lysine also contributes one novel strong saline interaction and both substitutions may favor resistance to neutralizing antibodies. We also investigated how the substitutions D614G, P681R, and P681H impact Spike structural conformations and discuss the impact of these changes to infectivity and lethality. The prevalent D614G substitution plays a key role in the communication between the glycine and the residues of a {beta}-strand located between the NTD and the RBD, impacting the transition between up- and down-RBD states. The P681R mutation, found in the Delta variant, favors intra- and inter-protomer correlations between the subunits S1 and S2. Conversely, in Omicron sub-variants, P681H decreases the intra- and inter-protomer long-range interactions within the trimeric Spike, providing an explanation for the reduced fusogenicity of this variant. Taken together, our results enhance the knowledge on how novel mutations lead to changes in infectivity and reveal mechanisms by which SARS-CoV-2 may evade the immune system.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.06.531335v1" target="_blank">Cooperative and structural relationships of the trimeric Spike with infectivity and antibody escape of the strains Delta (B.1.617.2) and Omicron (BA.2, BA.5, and BQ.1)</a>
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<li><strong>Immunometabolic rewiring in long COVID patients with chronic headache</strong> -
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<div>
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Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache. Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.06.531302v1" target="_blank">Immunometabolic rewiring in long COVID patients with chronic headache</a>
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</div></li>
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<li><strong>Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read scRNA-seq</strong> -
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Assessing the impact of SARS-CoV-2 variants on host immune systems is crucial with the continuous arrival of novel variants. However, there is a lack of reported studies utilizing single-cell RNA-sequencing (scRNA-seq) to elucidate the age-dependent host-viral interactions with different SARS-CoV-2 strains. Therefore, we employed Full-Length Transcriptome Sequencing (FLT-Seq) combining Illumina and Oxford Nanopore Technologies (ONT) with 10X 3-prime single cell sequencing to investigate host transcriptomic changes during wild-type (WT) and Alpha-strain SARS-CoV-2 infections within air-liquid-interface (ALI)-cultured human nasal epithelial cells from adults and adolescents. The results revealed increased innate immune responses in cells with lower viral loads which were lacking in cells with higher viral load. Alpha-infections showed heightened expression of genes related to interferon (IFN)-responses and protein-folding compared with WT, implying the increased immune response and endoplasmic reticulum stress with the variant of a higher transmission rate. ACE2 expression was elevated in infected populations of secretory and goblet cells with high IFN-stimulation and a subpopulation of ciliated cells but was lacking in bystander cells and other infected-cell types, despite detectable IFN-stimulation and regardless of strain. We used long-read sequencing to identify differential transcript usage (DTU) of IFN-response and translational genes, including IFI27, RPL4 and RPL15 (padj < 0.05) in infected cells compared with control, and consistent DTU of RPL15 and MX1 between Alpha and WT strain-infected cells in various cell-types. Together, these results reveal the dynamic transcriptional/translational/post-translational activity upon SARS-CoV-2 infection, which appeared to be age and strain-dependent. Overall, this study highlights the complexity of cell-type, age and viral-strain-dependent host epithelial responses to SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.04.531075v1" target="_blank">Uncovering strain- and age- dependent differences in innate immune response to SARS-CoV-2 infection in nasal epithelia using combined short and long-read scRNA-seq</a>
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<li><strong>An Integrative Approach to Dissect the Drug Resistance Mechanism of the H172Y Mutation of SARS-CoV-2 Main Protease</strong> -
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Nirmatrelvir is an orally available inhibitor of SARS-CoV-2 main protease (Mpro) and the main ingredient of PAXLOVID, a drug approved by FDA for high-risk COVID-19 patients. Recently, a rare natural mutation, H172Y, was found to significantly reduce nirmatrelvir’s inhibitory activity. As the COVID-19 cases skyrocket in China and the selective pressure of antiviral therapy builds up in the US, there is an urgent need to characterize and understand how the H172Y mutation confers drug resistance. Here we investigated the H172Y Mpro’s conformational dynamics, folding stability, catalytic efficiency, and inhibitory activity using all-atom constant pH and fixed-charge molecular dynamics simulations, alchemical and empirical free energy calculations, artificial neural networks, and biochemical experiments. Our data suggests that the mutation significantly weakens the S1 pocket interactions with the N-terminus and perturbs the conformation of the oxyanion loop, leading to a decrease in the thermal stability and catalytic efficiency. Importantly, the perturbed S1 pocket dynamics weakens the nirmatrelvir binding in the P1 position, which explains the decreased inhibitory activity of nirmatrelvir. Our work demonstrates the predictive power of the combined simulation and artificial intelligence approaches, and together with biochemical experiments they can be used to actively surveil continually emerging mutations of SARS-CoV-2 Mpro and assist the discovery of new antiviral drugs. The presented workflow can be applicable to characterize mutation effects on any protein drug targets.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.31.502215v2" target="_blank">An Integrative Approach to Dissect the Drug Resistance Mechanism of the H172Y Mutation of SARS-CoV-2 Main Protease</a>
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</div></li>
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<li><strong>Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</strong> -
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Background: Respiratory disease is a major cause of morbidity and mortality; however, current surveillance for circulating respiratory viruses is passive and biased. Seasonal circulation of respiratory viruses changed dramatically during the COVID-19 pandemic. More active methods for understanding respiratory disease dynamics are needed to better inform public health response and to guide clinical decision making. Wastewater-based epidemiology has been used to understand COVID-19, influenza A, and RSV infection rates at a community level, but has not been used to investigate other respiratory viruses. Methods: We measured concentrations of influenza A and B, RSV A and B, human parainfluenza (1-4), rhinovirus, seasonal human coronaviruses, and human metapneumovirus RNA in wastewater solids three times per week for 17 months spanning the COVID-19 pandemic at a wastewater treatment plant in California, USA. Novel probe-based assays were developed and validated for non-influenza viral targets. We compared viral concentrations to positivity rates for viral infections from clinical specimens submitted to sentinel laboratories. Findings: We detected RNA from all target viruses in wastewater solids. Human rhinovirus and seasonal coronaviruses were found at highest concentrations. Concentrations of viruses correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories. Measurements from wastewater indicated limited circulation of RSV A and influenza B, and human coronavirus OC43 dominated the seasonal human coronavirus infections while human parainfluenza 1 and 4A dominated among parainfluenza infections. Interpretation: Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 hours of sample collection, allowing real time information to inform public health response, clinical decision making, and individual behavior modifications.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280218v2" target="_blank">Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</a>
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<li><strong>The significant yet short-term influence of research covidization on journal citation metrics</strong> -
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COVID-19 has emerged as a significant research hotspot in recent years, leading to a surge in production and citations received by COVID-19 papers. While concerns have been raised about the potential citation boost on journals associated with publishing COVID-19 papers, the extent and mechanisms of such boost remain unclear. This study uses a generalized difference-in-differences approach to examine the impact of publishing COVID-19 papers on journal citations and related metrics in four highly covidized fields. Our results demonstrate that in health sciences fields, journals starting to publish COVID-19 papers in 2020 experienced a significant increase in citations compared with other journals. This trend continued in 2021, although to a lesser extent. However, such citation premiums became insignificant for journals starting to publish COVID-19 papers in 2021. In some fields, we also observed that COVID-19 papers increased the citations of non-COVID-19 papers in the same journals, but only for journals starting to publish COVID-19 papers in 2020. Our heterogeneity test indicates that COVID-19 papers published in prestigious journals brought more significant citation premiums to the journals and non-COVID-19 papers in most fields. We finally show that these citation premiums can affect various citation-based journal metrics. Our findings reveal a “gold rush” pattern in which early entrants are more likely to establish their citation advantage in research hotspots and caution against using such metrics to evaluate journal quality.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.05.531213v1" target="_blank">The significant yet short-term influence of research covidization on journal citation metrics</a>
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<li><strong>Predicting the feasibility of targeting a conserved region on the S2 domain of the SARS-CoV-2 spike protein</strong> -
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The efficacy of vaccines against the SARS-CoV-2 virus significantly declines with the emergence of mutant strains, prompting investigation into the feasibility of targeting highly conserved but often cryptic regions on the S2 domain of spike protein. Using tools from molecular dynamics, we find that this conserved S2 epitope located in the central helices below the receptor binding domains is unlikely to be exposed by dynamic fluctuations without any external facilitating factors, in spite of previous computational evidence suggesting transient exposure of this region. Furthermore, glycans inhibit opening dynamics, and thus stabilize spike in addition to immunologically shielding the protein surface, again in contrast to previous computational findings. Though the S2 epitope region examined here is central to large scale conformational changes during viral entry, free energy landscape analysis obtained using the path coordinate formalism reveals no inherent “loaded spring’” effect, suggesting that a vaccine immunogen would tend to present the epitope in a pre-fusion-like conformation and may be effective in neutralization. These findings contribute to a deeper understanding of the dynamic origins of the function of the spike protein, as well as further characterizing the feasibility of the S2 epitope as a therapeutic target.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.05.531227v1" target="_blank">Predicting the feasibility of targeting a conserved region on the S2 domain of the SARS-CoV-2 spike protein</a>
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<li><strong>Campus Sewage Water Surveillance based dynamics and infection trends of SARS-CoV-2 variants during third wave of COVID-19 in Pune, India</strong> -
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The wastewater-based epidemiology (WBE) of SARS-CoV-2 is a quick and cost-effective method of tracking virus transmission. However, few studies reported on campus or in academic or residential settings worldwide. In this study, we demonstrated the WBE approach to detect, monitor, and evaluate genomic variants of SARS-CoV-2 fragments in a sewage treatment plant (STP) located on the campus of CSIR National Chemical Laboratory, Pune, India. Herein we describe the early warning capability of WBE, with viral load rise in campus sewage water up to 14 days before its clinical detection. This was supported further by a significant correlation between SARS-CoV-2 RNA concentration and clinically reported COVID-19 cases on campus. Additionally, we comprehended the probable targets missed by the quantitative qRT-PCR using amplicon-based sequencing due to low viral load. The analysis revealed the presence of signature mutations of the Omicron (S:N679K, S:N764K, S:D796Y, N:P13L, ORF1a:T3255I, ORF1a:K856R, ORF1a:P3395H, and N:S413R) before the lineage was first detected globally. Further, we used Lineage decomposition (LCS) tool to detect the Variant of Concern (VOC)/Variant of Interest (VOI) signals upto a month earlier in sewage water samples. The analysis also indicated the transition of lineage from Delta to Omicron in late Decemeber,2021. This is the first study in India highlighting the use of on-campus STP to evaluate the local spread of SARS-CoV-2, which could aid in preventing COVID-19 in academic institutes/universities. This study proves the usefulness of WBE as an early warning system for detecting, tracking and tracing VOCs using the sequencing approach. The current study could aid in taking critical decisions to tackle the pandemic scenario on campus.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286683v2" target="_blank">Campus Sewage Water Surveillance based dynamics and infection trends of SARS-CoV-2 variants during third wave of COVID-19 in Pune, India</a>
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<li><strong>Convergent Evolution of A-Lineage (Clade 19B) SARS-CoV-2 Spike Sequences with B-Lineage Variants of Concern Affects Virus Replication in a Temperature-Dependent Manner on Human Nasal Epithelial Cell Cultures</strong> -
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The first three months of the COVID-19 pandemic was dominated by two SARS-CoV-2 lineages: A-lineages (Clade 19B) and B-lineages (Clade 19A). However, with the emergence of the Spike D614G substitution in B.1 lineages (Clade 20A), both early lineages were outcompeted and remained near-extinction from mid-2020 onwards. In early-2021, there was a re-emergence and persistence of novel A-lineage variants with substitutions in the Spike gene resembling those found in Variants of Concern (VOCs). An early A.3 variant (MD-HP00076/2020) and three A.2.5 variants (MD-HP02153/2021, MD-HP05922/2021 and CA-VRLC091/2021) were isolated and characterized for their genomic sequences, antibody neutralization, and in vitro replication. All A.2.5 isolates had five Spike mutations relative to the A.3 variant sequence: D614G, L452R, {Delta}141-143, D215A, and ins215AGY. Plaque reduction neutralization assays demonstrated that A.2.5 isolates had a 2.5 to 5-fold reduction in neutralization using contemporaneous COVID-19 convalescent plasma when compared to A.3. In vitro viral characterization in VeroE6 cell lines revealed that the A.3 isolate grew faster and spread more than A.2.5. On VeroE6-TMPRSS2 cells, significant syncytia formation was also observed with the A.2.5 isolates, however Spike cleavage efficiency did not explain these differences. In human nasal epithelial cell (hNEC) cultures, the A.2.5 isolates grew significantly faster and to higher total infectious virus titers than A.3. All A.2.5 lineage isolates grew significantly faster at 37{degrees}C than at 33{degrees}C irrespective of cell type, and to higher peak titers except compared to A.3. This suggests A.2.5’s adapted to improve replication using similar mutations found in the B-lineage SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.03.531067v1" target="_blank">Convergent Evolution of A-Lineage (Clade 19B) SARS-CoV-2 Spike Sequences with B-Lineage Variants of Concern Affects Virus Replication in a Temperature-Dependent Manner on Human Nasal Epithelial Cell Cultures</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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise<br/><b>Sponsor</b>: Basma Mosaad Abd-elrahman Abushady<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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 in the Post-COVID-19 Patient (TRIALS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Istituto Auxologico Italiano<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>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical 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>Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine</strong> - <b>Conditions</b>: Vaccine Reaction; COVID-19<br/><b>Interventions</b>: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<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 of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo<br/><b>Sponsor</b>: Westlake Pharmaceuticals (Hangzhou) 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>ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo<br/><b>Sponsors</b>: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.<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>A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan 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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2 Trial of the Immunogenicity and Safety of CVXGA1 Intranasal COVID Vaccine in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: CVXGA1<br/><b>Sponsor</b>: CyanVac LLC<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory activity of a sulfated oligo-porphyran from Pyropia yezoensis against SARS-CoV-2</strong> - COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-β-d-Gal-(1 → 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more…</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 diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics</strong> - In December 2019, the global coronavirus disease 2019 (COVID-19) pandemic began in Wuhan, China. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells primarily through the angiotensin-converting enzyme 2 (ACE2) receptor. In addition to ACE2, several studies have shown the importance of heparan sulfate (HS) on the host cell surface as a co-receptor for SARS-CoV-2-binding. This insight has driven research into antiviral therapies, aimed…</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>Work-related experiences of consultant psychiatrists during the COVID-19 response: qualitative analysis</strong> - CONCLUSIONS: The challenges of leading mental health services were evident in the increased complexity involved in caring for vulnerable patients during the pandemic, contributing to uncertainty, loss of control and moral distress among participants. These dynamics worked synergistically with pre-existing system-level failures, eroding capacity to mount an effective response. The longer-term psychological well-being of consultant psychiatrists - as well as the pandemic preparedness of healthcare…</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>Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection</strong> - ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low hanging fruit for combatting SARS-CoV-2?</strong> - Entry of SARS-CoV-2 into human respiratory cells, mediated by the spike protein, is absolutely dependent on the cellular receptor ACE2 (angiotensin-converting enzyme-2). This makes ACE2 an attractive target for therapeutic intervention in COVID-19. In this issue, Zuo et al. discover that vitamin C, an essential nutrient and common dietary supplement, can target ACE2 for ubiquitin-dependent degradation, resulting in the inhibition of SARS-CoV-2 infection (Zuo et al, 2023). The study identifies…</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>Comparison of Anakinra and Tocilizumab in Anticytokine Therapy in the Treatment of Coronavirus Disease-2019</strong> - CONCLUSION: We observed the positive effects of the use of tocilizumab on clinical improvement in the early period; mechanical ventilation requirement was delayed and at a lower rate. Anakinra treatment did not change mortality and PaO(2)/FiO(2) rates. Mechanical ventilation requirements occurred earlier in the patients who were not receiving any anticytokine therapy. Studies with larger patient populations are needed to demonstrate the potential efficacy of anticytokine therapy.</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>Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in <em>Cordyceps militaris</em></strong> - Cordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity</strong> - CONCLUSION: Increased mRNA vaccine dosing intervals longer than 38 days result in higher levels of anti-spike antibodies and ACE-2 inhibition when assessed six months after the first COVID-19 vaccine.</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><em>In vitro</em> metabolic characterization of the SARS-CoV-2 papain-like protease inhibitors GRL0617 and HY-17542</strong> - The SARS-CoV-2 pandemic requires a new therapeutic target for viral infection, and papain-like protease (Plpro) has been suggested as a druggable target. This in-vitro study was conducted to examine the drug metabolism of the GRL0617 and HY-17542, Plpro inhibitors. Metabolism of these inhibitors was studied to predict the pharmacokinetics in human liver microsomes. The hepatic cytochrome P450 (CYP) isoforms responsible for their metabolism were identified using recombinant enzymes. The drug-drug…</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>Polypropylene Modified with Ag-Based Semiconductors as a Potential Material against SARS-CoV-2 and Other Pathogens</strong> - The worldwide outbreak of the coronavirus pandemic (COVID-19) and other emerging infections are difficult and sometimes impossible to treat, making them one of the major public health problems of our time. It is noteworthy that Ag-based semiconductors can help orchestrate several strategies to fight this serious societal issue. In this work, we present the synthesis of α-Ag(2)WO(4), β-Ag(2)MoO(4), and Ag(2)CrO(4) and their immobilization in polypropylene in the amounts of 0.5, 1.0, and 3.0 wt %,…</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>Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature</strong> - CONCLUSION: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.</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 Pharmacodynamics of Imatinib for Optimal Drug Repurposing from Cancer to COVID-19</strong> - CONCLUSION: COVID-19 patients exhibit higher total imatinib exposure compared to cancer patients, attributed to differences in plasma protein concentrations. Higher imatinib exposure in COVID-19 patients did not associate with improved clinical outcomes. Total C(trough) and AUC(ave) inversely associated with some PD-outcomes, which may be biased by disease course, variability in metabolic rate and protein binding. Therefore, additional PKPD analyses into unbound imatinib and its main metabolite…</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>Establishment of angiotensin-converting enzyme 2 and cluster of differentiation 147 dual target cell membrane chromatography based on SNAP-tag technology for screening anti severe acute respiratory syndrome coronavirus 2 active components</strong> - Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147…</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>Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides</strong> - Development of potent and broad-spectrum antivirals against SARS-CoV-2 remains one of top priorities, especially in the case of that current vaccines cannot effectively prevent viral transmission. We previously generated a group of fusion-inhibitory lipopeptides, with one formulation being evaluated under clinical trials. In this study, we dedicated to characterize the extended N-terminal motif (residues 1161-1168) of the so-called spike (S) heptad repeat 2 (HR2) region. Alanine scanning…</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>Pinosrtobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism</strong> - Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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