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193 lines
48 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>31 May, 2022</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>Agreeableness and neuroticism predict being more concerned about COVID-19 and bothered by friends’ risky behavior</strong> -
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Given the importance of friendships during challenging times and the mixed associations reported between personality traits and disease-related behaviors, we investigated the influence of personality traits on friendships during the COVID-19 pandemic and how both influenced risky behaviors. In November 2020, we asked participants about their reactions to friends’ behavior as part of a larger study. We found that agreeableness and neuroticism predicted participants being more concerned about COVID-19 and bothered by friends’ risky behavior, and extraversion predicted enjoying helping friends during the pandemic. Our results suggest that personality influences how individuals cope with their friends’ risky behaviors. This work could be relevant for developing interventions to reduce risk-taking during the pandemic, such as using friendships to reinforce adherence to public health guidelines.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/qkp8b/" target="_blank">Agreeableness and neuroticism predict being more concerned about COVID-19 and bothered by friends’ risky behavior</a>
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<li><strong>Incidence of SARS-CoV-2 infection among unvaccinated US adults during the Omicron wave</strong> -
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As of 4/20/2022, approximately 23% of the eligible US population was unvaccinated. We studied COVID-19 infections during the Omicron (B.1.1.529) wave in unvaccinated US adults, stratified by pre-Omicron antibody levels. Anti-spike serologic testing was performed prior to the Omicron wave in the United States (9/23/21-11/5/21) and participants were surveilled to determine incident COVID-19. Only 12% of those who entered the wave with antibodies reported a test-confirmed COVID-19 infection, compared to 35% of those without antibodies prior to the Omicron wave. Effectiveness of these anti-RBD antibodies in this unvaccinated population was 67%. Among people with antibodies, titer did not appear to be associated with risk of test-confirmed Omicron infection.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.27.22275630v1" target="_blank">Incidence of SARS-CoV-2 infection among unvaccinated US adults during the Omicron wave</a>
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</div></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression</strong> -
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The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 500 million infections and more than six million deaths worldwide. Although the viral genomes of SARS-CoV-1 and SARS-CoV-2 share high sequence homology, the clinical and pathological features of COVID-19 differ profoundly from those of SARS. It is apparent that changes in viral genes contribute to the increased transmissibility of SARS-CoV-2 and pathology of COVID-19. Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, mediated by recognition of virus-derived peptides that are presented on MHC class I molecules. Here, we show that SARS-CoV-2 can interfere with antigen presentation thereby evading immune surveillance. SARS-CoV-2 infection of monkey and human cell lines resulted in reduced cell-surface expression of MHC class I molecules. We identified a single viral gene product, the accessory factor open reading frame 7a (ORF7a), that mediates this effect. ORF7a interacts with HLA class I molecules in the ER, resulting in ER retention or impaired HLA heavy chain (HC) trafficking to the Golgi. Ultimately, these actions result in reduced HLA class I surface expression on infected cells. Whereas ORF7a from SARS-CoV-2 reduces surface HLA class I levels, the homologous ORF7a from the 2002 pandemic SARS-CoV-1 did not, suggesting that SARS-CoV-2 ORF7a acquired the ability to downregulate HLA-I during evolution of the virus. We identified a single amino acid in the SARS-CoV-1 ORF7a luminal domain that, upon mutating to the corresponding SARS-CoV-2 ORF7a sequence, induced a gain-of-function in HLA surface downregulation. By abrogating HLA class I antigen presentation via ORF7a, SARS-CoV-2 may evade host immune responses by inhibiting anti-viral cytotoxic T cell activity, thereby contributing to the pathology of COVID-19.
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</ul>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.29.493850v1" target="_blank">The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression</a>
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</div>
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<li><strong>Specifying uniform eligibility criteria to strengthen causal inference studies of long-term outcomes of COVID-19</strong> -
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Background: Causal interpretation of findings from existing epidemiological studies on long-term clinical outcomes of coronavirus disease 2019 (COVID-19) may be limited by the choice of comparator (control) group. Objective: We compare two approaches to control group selection (based on requirement for negative SARS-CoV-2 test for eligibility) in long-term clinical outcomes after COVID-19 in patients with history of heart failure (HF). Design: Retrospective cohort study using data from February 1, 2020 to July 31, 2021. Setting: Veteran Health Administration (VHA). Participants: We studied two cohorts of Veterans with COVID-19 and history of HF which selected comparison group using two different approaches. In Cohort I, Veterans with HF who tested for positive for SARS-CoV-2 were age, sex, and race matched to Veterans with no evidence of COVID-19 in 1:5 ratio. In Cohort II Veterans with HF who tested positive for SARS-CoV-2 were age, sex, and race matched with Veterans with HF who tested negative for SARS-CoV-2 within +/-15 days of the positive test date within the same VHA facility. Exposure: COVID-19 as determined by a positive SARS-CoV-2 test. Main Outcomes and Measures: 1-year all-cause mortality and hospital admissions beyond the first 30 days after COVID-19 diagnosis. Adjusted hazard ratios (HRs) accounting for comorbidity and 95% confidence intervals were calculated. Results: Cohort I comprised 13,722 Veterans with HF with COVID-19 (mean [SD] age 72.0 [10.2] years, 2.4% female, 71.1% White) and 60,956 matched controls not known to have COVID-19. Cohort II comprised 6,725 Veterans with HF with COVID-19 (mean [SD] age 72.5 [7.5] years, 0.1% female, 80.8% White) and 6,726 matched controls with negative SARS- CoV-2 test. The adjusted HRs for 1-year mortality and hospital admission beyond the first 30 days after diagnosis of COVID-19 were 1.40 (1.32-1.49) and 1.34 (1.28-1.41), respectively, in analysis of Cohort-I (where the comparator group was not required to test negative for SARS-CoV-2). However, in Cohort-II (using the second comparator group specifying negative SARS-CoV-2 test for eligibility), the associations were markedly attenuated; adjusted HRs 1.05 (0.95-1.17) and 1.07 (0.96-1.19), respectively. Conclusions: We found significant attenuation of associations between COVID-19 and long- term risk of mortality and hospital admissions beyond the first 30 days among patient with existing HF, when comparing with a control group selected based on a negative SARS-CoV-2 test versus control group not known to have COVID-19. The findings have implications for the design of studies of long-term CVD (and non-CVD) outcome of COVID-19.
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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/10.1101/2022.05.30.22275733v1" target="_blank">Specifying uniform eligibility criteria to strengthen causal inference studies of long-term outcomes of COVID-19</a>
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<li><strong>Increased ambulance attendances related to suicide and self-injury in response to the pandemic</strong> -
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Investigating the change in the trend of ambulance service utilization for suicide in response to the COVID-19 pandemic can clarify the impact of the pandemic on acute healthcare services. To determine whether the trends of the ambulance attendances related to self-injury and suicide changes in response to the COVID-19 pandemic. We extracted the data from the National Ambulance Surveillance System in Australia between March 2018 and March 2021 to examine the trajectory of the ambulance attendances related to self-injury and suicide. The results indicate that the number of ambulance attendances related to self-injury, suicidal ideation and suicidal attempt increased immediately during the first quarter since the outbreak and stayed higher over the at least 12 months. Notably, the post-outbreak surge in ambulance attendances associated with these mental health crises did not continue to escalate further. To sum up, the overall increase in ambulance attendances may reflect increased distress in the community, but also signify disruptions of other non-emergency health services. In contrast to recent evidence for the suicide rate being unchanged during the pandemic, our findings provide a different perspective on the impact of the pandemic on mental health services. This warrants a re-assessment of resources for mental health services in the post-COVID era.
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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/10.1101/2022.05.29.22273082v1" target="_blank">Increased ambulance attendances related to suicide and self-injury in response to the pandemic</a>
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<li><strong>Governance is key to controlling SARS-CoV-2’s vaccine resistance</strong> -
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Little attention has been paid to governance9s impacts on the evolution of SARS-CoV-2, the virus that causes COVID-19. To evaluate such impacts on the evolution of vaccine resistance, we analyzed a stochastic compartmental model to quantify the risk a mutant strain capable of evading immunity emerges post-vaccine rollout. We calibrated the model with publicly available data for four territories in the Western Hemisphere qualitatively differing in pandemic interventions. The model shows an immune-evading strain to be readily selected over all infectivities in Texas. In Panama, only a high level of transmission permits immune evasion to evolve. No invasion appears likely in Costa Rica and Uruguay. Programs combining pharmaceutical and nonpharmaceutical interventions are best positioned to remove the epidemiological space SARS-CoV-2 needs to evolve vaccine resistance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.26.22275649v1" target="_blank">Governance is key to controlling SARS-CoV-2’s vaccine resistance</a>
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<li><strong>Investigation of a SARS-CoV-2 outbreak in a Texas summer camp resulting from a single introduction</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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SARS-CoV-2 is the etiological agent responsible for the COVID-19 pandemic. It is estimated that only 10 aerosol- borne virus particles are sufficient to establish a secondary infection with SARS-CoV-2. However, the dispersal pattern of SARS-CoV-2 is highly variable and only 10-20% of cases are responsible for up 80% of secondary infections. The heterogeneous nature of SARS-CoV-2 transmission suggests that super-spreader events play an important role in viral transmission. Super-spreader events occur when a single person is responsible for an unusually high number of secondary infections due to a combination of biological, environmental, and/or behavioral factors. While super-spreader events have been identified as a significant factor driving SARS-CoV-2 transmission, epidemiologic studies have consistently shown that education settings do not play a major role in community transmission. However, an outbreak of SARS-CoV-2 was recently reported among 186 children (aged 10-17) and adults (aged 18 +) after attending an overnight summer camp in Texas in June 2021. To understand the transmission dynamics of the outbreak, RNA was isolated from 36 nasopharyngeal swabs collected from patients that attended the camp and 19 control patients with no known connection to the outbreak. Genome sequencing on the Oxford Nanopore platform was performed using the ARTIC approaches for library preparation and bioinformatic analysis. SARS-CoV-2 amplicons were produced from all RNA samples and >70% of the viral genome was successfully reconstructed with >10X coverage for 46 samples. Phylogenetic methods were used to estimate the transmission history and suggested that the outbreak was the result of a single introduction. We also found evidence for secondary transmission from campers to the community. Together, these findings demonstrate that super-spreader events may occur during large gatherings of children.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.29.22275277v1" target="_blank">Investigation of a SARS-CoV-2 outbreak in a Texas summer camp resulting from a single introduction</a>
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<li><strong>Incidence of Post-Covid Syndrome and Associated Symptoms in Outpatient Care in Bavaria, Germany</strong> -
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Objectives: To estimate the treatment incidence of Post-Covid Syndrome in the context of office-based care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19. Design: Retrospective analysis of routinely collected claims data. Setting: Office-based care in Bavaria, Germany. Participants: 391,990 patients with confirmed COVID-19 diagnosis, 62,659 patients with other respiratory infection, and a control group of 659,579 patients with no confirmed or suspected diagnosis COVID-19. Primary and Secondary Outcome Measures: Primary outcome is diagnosis of a Post-COVID Syndrome by an office-based physician. Secondary outcomes are: Chronic Fatigue Syndrome (CFS), psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnea, pulmonary embolism and myalgia. Results: Among all patients with confirmed COVID-19 infection, 14.2% (95% CI: 14.0-14.5) received a diagnosis of a Post-COVID Syndrome, and 6.7% (6.5-6.9) received the diagnosis in at least two quarterly periods during a two-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including CFS (1.6% vs. 0.6% and 0.3%, respectively), fatigue (13.3% vs. 9.2% and 6.0%), dyspnea (9.9% vs. 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs. 1.2% and 0.5%). The treatment incidence of Post-COVID Syndrome was highest among adults aged 40-59 (19.0%) and lowest among children aged below 12 years (2.6%). Conclusions: Our results demonstrate a moderately high incidence of Post-COVID Syndrome two years after infection with COVID-19. There is an urgent need to find efficient and effective solutions to help patients with mental disorders, dyspnea, fatigue and loss of smell. Guidelines and treatment algorithms, including referral criteria, occupational and physical therapy, require promptly and coherent implementation. Further research is required both to find new therapeutic options and to assess the implications of Post-COVID Syndrome for health services.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.29.22275262v1" target="_blank">Incidence of Post-Covid Syndrome and Associated Symptoms in Outpatient Care in Bavaria, Germany</a>
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<li><strong>Recoverability of Ancestral Recombination Graph Topologies</strong> -
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Recombination is a powerful evolutionary process that shapes the genetic diversity observed in the populations of many species. Reconstructing genealogies in the presence of recombination from sequencing data is a very challenging problem, as this relies on mutations having occurred on the correct lineages in order to detect the recombination and resolve the ordering of coalescence events in the local trees. We investigate the probability of reconstructing the true topology of ancestral recombination graphs (ARGs) under the coalescent with recombination and gene conversion. We explore how sample size and mutation rate affect the inherent uncertainty in reconstructed ARGs, which sheds light on the theoretical limitations of ARG reconstruction methods. We illustrate our results using estimates of evolutionary rates for several organisms; in particular, we find that for parameter values that are realistic for SARS-CoV-2, the probability of reconstructing genealogies that are close to the truth is low.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.10.463724v2" target="_blank">Recoverability of Ancestral Recombination Graph Topologies</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The U.S. academic job market survives the SARS-CoV-2 global pandemic</strong> -
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Many speculated that the faculty job market would be severely impacted by the COVID-19 pandemic, potentially for years. Our examination of faculty job postings from 2018 to 2021 found that while they decreased in 2020, the market recovered in 2021. We also surveyed how the pandemic affected the perceptions, behaviors, and outcomes of individuals on the faculty job market in 2019 to 2020 and 2020 to 21. Approximately 10% of the faculty job offers made to 2019 through 2020 survey respondents were reported as rescinded. Respondents also reported altering their application documents in response to the pandemic as well as delaying or even abandoning their faculty job search. Thus, while the faculty job market may have recovered, the effect of the pandemic on postdoctoral career choices may have future implications.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.27.493714v1" target="_blank">The U.S. academic job market survives the SARS-CoV-2 global pandemic</a>
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<li><strong>Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge</strong> -
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The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to the insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp promotes a tripartite immunity consisting of systemic, cellular and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.29.493866v1" target="_blank">Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge</a>
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<li><strong>Potentiating the cross-reactive IFN-γ T cell and polyfunctional T cell responses by heterologous GX-19N DNA booster in mice primed with either a COVID-19 mRNA vaccine or inactivated vaccine</strong> -
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Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potentials of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T-cells to the SARS-CoV-2 variant of concern (VOC) compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T-cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.29.493923v1" target="_blank">Potentiating the cross-reactive IFN-γ T cell and polyfunctional T cell responses by heterologous GX-19N DNA booster in mice primed with either a COVID-19 mRNA vaccine or inactivated vaccine</a>
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<li><strong>Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro</strong> -
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SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its ~30 kb RNA genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro/nsp5). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-10/11 polyprotein, whose mature products are cofactors of the viral replicase, identifying the order of cleavages as: 1) nsp9-10, 2) nsp8-9/nsp10-11, and 3) nsp7-8. Integrative modeling based on mass spectrometry (including hydrogen- deuterium exchange and cross-linking) and X-ray scattering yielded three-dimensional models of the nsp7-10/11 polyprotein. Our data suggest that the nsp7-10/11 structure in complex with Mpro strongly resembles the unbound polyprotein, and that both polyprotein conformation and junction accessibility determine the preference and order of cleavages. Finally, we used limited proteolysis assays to characterize the effect of a series of inhibitors/binders on Mpro processing of nsp7-11 and Mpro inhibition using a polyprotein substrate.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.27.493767v1" target="_blank">Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro</a>
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<li><strong>Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations</strong> -
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The search for drugs against COVID-19 and other diseases caused by coronaviruses focuses on the most conserved and essential proteins, mainly the main (Mpro) and the papain-like (PLpro) proteases and the RNA-dependent RNA polymerase (RdRp). Nirmatrelvir, an inhibitor for Mpro, was recently approved by FDA as a part of a two-drug combination, Paxlovid, and many more drugs are in various stages of development. Multiple candidates for the PLpro inhibitors are being studied, but none have yet progressed to clinical trials. Several repurposed inhibitors of RdRp are already in use. We can expect that once anti-COVID-19 drugs become widely used, resistant variants of SARS-CoV-2 will emerge, and we already see that for the drugs targeting SARS-CoV-2 RdRp. We hypothesize that emergence of such variants can be anticipated by identifying possible escape mutations already present in the existing populations of viruses. Our group previously developed the coronavirus3D server (https://coronavirus3d.org), tracking the evolution of SARS- CoV-2 in the context of the three-dimensional structures of its proteins. Here we introduce dedicated pages tracking the emergence of potential drug resistant mutations to Mpro and PLpro, showing that such mutations are already circulating in the SARS- CoV-2 viral population. With regular updates, the drug resistance tracker provides an easy way to monitor and potentially predict the emergence of drug resistance-conferring mutations in the SARS-CoV-2 virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.27.493798v1" target="_blank">Monitoring for SARS-CoV-2 drug resistance mutations in broad viral populations</a>
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<li><strong>Modelling patterns of SARS-CoV-2 circulation in the Netherlands, August 2020-February 2022, revealed by a nationwide sewage surveillance program</strong> -
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SUMMARY Background Surveillance of SARS-CoV-2 in wastewater offers an unbiased and near real-time tool to track circulation of SARS-CoV-2 at a local scale, next to other epidemic indicators such as hospital admissions and test data. However, individual measurements of SARS-CoV-2 in sewage are noisy, inherently variable, and can be left-censored. Aim We aimed to infer latent virus loads in a comprehensive sewage surveillance program that includes all sewage treatment plants (STPs) in the Netherlands and covers 99.6% of the Dutch population. Methods A multilevel Bayesian penalized spline model was developed and applied to estimate time- and STP-specific virus loads based on water flow adjusted SARS- CoV-2 qRT-PCR data from 1-4 sewage samples per week for each of the >300 STPs. Results The model provided an adequate fit to the data and captured the epidemic upsurges and downturns in the Netherlands, despite substantial day-to-day measurement variation. Estimated STP virus loads varied by more than two orders of magnitude, from approximately 1012 (virus particles per 100,000 persons per day) in the epidemic trough in August 2020 to almost 1015 in many STPs in January 2022. Epidemics at the local levels were slightly shifted between STPs and municipalities, which resulted in less pronounced peaks and troughs at the national level. Conclusion Although substantial day-to-day variation is observed in virus load measurements, wastewater-based surveillance of SARS-CoV-2 can track long-term epidemic progression at a local scale in near real-time, especially at high sampling frequency.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275569v1" target="_blank">Modelling patterns of SARS-CoV-2 circulation in the Netherlands, August 2020-February 2022, revealed by a nationwide sewage surveillance program</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Hymecromone tablets; Other: Placebo<br/><b>Sponsor</b>: Shanghai Zhongshan Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>: <br/>
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University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB<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 Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir<br/><b>Sponsor</b>: Pfizer<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>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<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 Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: DXP604<br/><b>Sponsor</b>: <br/>
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Wuhan Institute of Biological Products 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>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant); Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)<br/><b>Sponsor</b>: <br/>
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Sinovac Research and Development 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>A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma 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>INTEGrating Ag-RDTs for COVID in MNCH,HIV and TB Services in Cameroon and Kenya:A Cluster Randomized Trial of Two Models</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Test all<br/><b>Sponsors</b>: <br/>
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Elizabeth Glaser Pediatric AIDS Foundation; UNITAID; Kenya Ministry of Health; Ministry of Public Health, Cameroon<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>Pulmonary Rehabilitation Program With Pulsed Electromagnetic Field Therapy in Patients With Post-covid Sequelae.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Pulsed ectromagnetid field therapy; Other: Pulmonary rehabilitation program (PRP)<br/><b>Sponsor</b>: University of Malaga<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: Coronavirus Disease 2019 (COVID-19)<br/><b>Intervention</b>: Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])<br/><b>Sponsor</b>: AstraZeneca<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>Inhaled Interferon α2b Treatment in Mild-to-moderate COVID-19 Infected Children</strong> - <b>Conditions</b>: COVID-19; Children<br/><b>Interventions</b>: Drug: Inhaled Interferon α2b; Other: Standard of Care<br/><b>Sponsors</b>: Children’s Hospital of Fudan University; RenJi Hospital; Shanghai Children’s Hospital; Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine<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>Paxlovid in the Treatment of COVID-19 Patients With Uremia</strong> - <b>Conditions</b>: COVID-19; Uremia<br/><b>Interventions</b>: Drug: Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telemedically Assisted Sampling of COVID-19 Patients - Is the Sampling Quality Sufficient</strong> - <b>Conditions</b>: Telemedicine; Pharynx; COVID-19<br/><b>Intervention</b>: Diagnostic Test: telemedically guided oropharyngeal + nasal (OP+N) self-sampling (GSS) and nasopharyngeal (NP) or OP+N sampling performed by health care professionals (HCP)<br/><b>Sponsor</b>: Teststation Praxis Dr. med Bielecki<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>Improving Pediatric COVID-19 Vaccine Uptake Using an mHealth Tool</strong> - <b>Conditions</b>: COVID-19 Vaccines; Telemedicine; Vaccine Hesitancy; Pediatric ALL<br/><b>Interventions</b>: Behavioral: COVID-19 Vaccine Uptake App; Other: General Health App<br/><b>Sponsors</b>: <br/>
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University of Arkansas; National Institutes of Health (NIH); University of Nebraska; University of Montana<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>Retraction: Jiang, H.; Mei, Y.-F. SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro. <em>Viruses</em> 2021, <em>13</em>, 2056</strong> - The published article […].</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>Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor</strong> - Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal…</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>Infectious Bronchitis Virus Nsp14 Degrades JAK1 to Inhibit the JAK-STAT Signaling Pathway in HD11 Cells</strong> - Coronaviruses (CoVs) are RNA viruses that can infect a wide range of animals, including humans, and cause severe respiratory and gastrointestinal disease. The Gammacoronavirus avian infectious bronchitis virus (IBV) causes acute and contagious diseases in chickens, leading to severe economic losses. Nonstructural protein 14 (Nsp14) is a nonstructural protein encoded by the CoV genome. This protein has a regulatory role in viral virulence and replication. However, the function and mechanism 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>SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions</strong> - This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Unique Robust Dual-Promoter-Driven and Dual-Reporter-Expressing SARS-CoV-2 Replicon: Construction and Characterization</strong> - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, SARS2) remains a great global health threat and demands identification of more effective and SARS2-targeted antiviral drugs, even with successful development of anti-SARS2 vaccines. Viral replicons have proven to be a rapid, safe, and readily scalable platform for high-throughput screening, identification, and evaluation of antiviral drugs against positive-stranded RNA viruses. In the study, we report a unique robust HIV long…</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 Six Serological Immunoassays for the Detection of SARS-CoV-2 Neutralizing Antibody Levels in the Vaccinated Population</strong> - Neutralizing antibody (NAb) detection is critical for evaluating herd immunity and monitoring the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, quantitative SARS-CoV-2 antibody levels after vaccination were measured by chemiluminescent immunoassays, enzyme immunoassays, and surrogate virus neutralization tests (sVNTs), as well as plaque reduction neutralization tests (PRNT). Sequential blood samples were collected before and 1 and 3…</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 Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses</strong> - New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many…</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>Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication</strong> - RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies…</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>Targeting of Silver Cations, Silver-Cystine Complexes, Ag Nanoclusters, and Nanoparticles towards SARS-CoV-2 RNA and Recombinant Virion Proteins</strong> - Background: Nanosilver possesses antiviral, antibacterial, anti-inflammatory, anti-angiogenesis, antiplatelet, and anticancer properties. The development of disinfectants, inactivated vaccines, and combined etiotropic and immunomodulation therapy against respiratory viral infections, including COVID-19, remains urgent. Aim: Our goal was to determine the SARS-CoV-2 molecular targets (genomic RNA and the structural virion proteins S and N) for silver- containing nanomaterials. Methods: 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>Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator</strong> - Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antimicrobial Biomaterial on Sutures, Bandages and Face Masks with Potential for Infection Control</strong> - Antimicrobial resistance (AMR) is a challenge for the survival of the human race. The steady rise of resistant microorganisms against the common antimicrobials results in increased morbidity and mortality rates. Iodine and a plethora of plant secondary metabolites inhibit microbial proliferation. Antiseptic iodophors and many phytochemicals are unaffected by AMR. Surgical site and wound infections can be prevented or treated by utilizing such compounds on sutures and bandages. Coating surgical…</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>Inclusion of a Phytomedicinal Flavonoid in Biocompatible Surface-Modified Chylomicron Mimic Nanovesicles with Improved Oral Bioavailability and Virucidal Activity: Molecular Modeling and Pharmacodynamic Studies</strong> - Morin hydrate (MH) is a widely-used Asian phytomedicinal flavonoid with a wide range of reported therapeutic activities. However, MH has limited oral bioavailability due to its low aqueous solubility and intestinal permeability, which in turn hinders its potential antiviral activity. The study reported herein was designed to encapsulate MH in polyethyleneglycolated (PEGylated) chylomicrons (PCMs) and to boost its antiviral activity and biological availability for oral administration using a rat…</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>Methylene Blue Is a Nonspecific Protein-Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19</strong> - We have previously identified methylene blue, a tricyclic phenothiazine dye approved for clinical use for the treatment of methemoglobinemia and for other medical applications as a small-molecule inhibitor of the protein-protein interaction (PPI) between the spike protein of the SARS-CoV-2 coronavirus and ACE2, the first critical step of the attachment and entry of this coronavirus responsible for the COVID-19 pandemic. Here, we show that methylene blue concentration dependently inhibits this…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of <em>Aronia melanocarpa</em> (Michx.) Elliot and <em>Sambucus nigra</em> L</strong> - Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double- standardized blend of extracts from Aronia…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Integrin/TGF-β1 Inhibitor GLPG-0187 Blocks SARS-CoV-2 Delta and Omicron Pseudovirus Infection of Airway Epithelial Cells In Vitro, Which Could Attenuate Disease Severity</strong> - As COVID-19 continues to pose major risk for vulnerable populations, including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins, either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate the blockade of SARS- CoV-2 pseudovirus infection of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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