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<title>13 April, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Should Health Communication During the SARS-CoV-2 Pandemic Emphasize Self- or Other-Focused Impacts of Mitigation Behaviors? Insights from Two Message Matching Studies</strong> -
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Mask-wearing, social distancing, and vaccination remain effective ways to mitigate the spread of COVID-19. Yet, many hesitate to enact some or all these preventive behaviors. We created three persuasive messages—framed to promote benefits to either 1) oneself, 2) close-others, or 3) distant-others—to determine whether the effectiveness of these messages varied based on personality differences (specifically independent/interdependent self-construal and chronic construal level). In two online experiments (N = 862), we measured individual differences and showed participants one of the three messages. Consistent interactions between interdependent self-construal and message conditions showed that those high in interdependent self-construal responded most positively to the self-focused messages promoting mask-wearing, social distancing, and COVID-19 vaccination. Those low in interdependent self-construal responded most negatively to the self-focused messages. Although no interaction effect was observed for independent self-construal, and inconsistent evidence emerged for construal level, other-focused messages performed either better or equally well to the self-focused messages for most participants and may thus be promising for future public health communication efforts.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2ysn5/" target="_blank">Should Health Communication During the SARS-CoV-2 Pandemic Emphasize Self- or Other-Focused Impacts of Mitigation Behaviors? Insights from Two Message Matching Studies</a>
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</div></li>
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<li><strong>Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab</strong> -
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Background: Little data exists to guide the treatment of persistent COVID-19 in immunocompromised patients. We have employed a unique protocol combining tixegavimab/cilgavimab, and short-term combination antivirals including remdesivir. Methods: A retrospective single-center analysis of persistent COVID-19 in immunocompromised patients. Response was assessed by symptom resolution, declining C-reactive protein (CRP) levels and increasing SARS-CoV-2-PCR cycle-threshold (Ct) values. Results: Fourteen patients were included, including 2 kidney transplant recipients, 11 with B-cell lymphoproliferative disease, treated with anti-CD20 or ibrutinib, and 1 with rheumatoid arthritis, treated with anti-CD20. Median Ct-value was 27 (interquartile range (IQR):24-32). All patients received tixegavimab/cilgavimab and a 5-day course of remdesivir. Eleven also received nirmaltrevir/ritonavir and one received molnupiravir. Median follow-up was 45 days (IQR:12-89). Eleven patients had complete responses including symptom resolution, decrease in CRP, and increase in Ct values (all with either a negative PCR or Ct value>30 on day 4-16). Three patients had a partial response with relapses requiring re-admission. One had died, and two responded to prolonged antiviral treatments. Conclusions: A combination of monoclonal antibodies with antivirals has led to complete resolution of persistent COVID-19 in most severely-immunocompromised patients. Controlled studies will further direct the treatment of these patients, while more effective antivirals are urgently needed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288144v1" target="_blank">Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab</a>
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</div></li>
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<li><strong>The COVID-19 vaccination campaign in Switzerland and its impact on disease spread</strong> -
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We analyse infectious disease case surveillance data stratified by region and age group to estimate COVID-19 spread and gain an understanding of the impact of introducing vaccines to counter the disease in Switzerland. The data used in this work is extensive and detailed and includes information on weekly number of cases and vaccination rates by age and region. Our approach takes into account waning immunity. The statistical analysis allows us to determine the effects of choosing alternative vaccination strategies. Our results indicate greater uptake of vaccine would have led to fewer cases with a particularly large effect on undervaccinated regions while an alternative distribution scheme ignoring age would affect the vulnerable population at the time (the elderly) and is less ideal.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.06.23288251v1" target="_blank">The COVID-19 vaccination campaign in Switzerland and its impact on disease spread</a>
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</div></li>
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<li><strong>A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Vaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.11.23288409v3" target="_blank">A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</a>
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</div></li>
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<li><strong>A gene-expression module in circulating immune cells is associated with cell migration during immune diseases.</strong> -
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Circulating immune cells are critical mediators of the response to inflammation upon recruitment to the tissue but how gene expression state influences recruitment is not well known. Here we report the longitudinal single-cell transcriptome profiling of blood mononuclear cells in patients undergoing kidney transplantation rejection. We identify a gene expression module which is associated to transcriptional regulation, homing and early activation in multiple cell types. The circulating cells expressing this module are reduced in patients undergoing graft rejection. This reduction was confirmed in a pig model of acute kidney transplantation rejection. In connection with this, the module expression drastically increased in the kidney grafts undergoing rejection indicating a preferential recruitment of cells highly expressing this module. We identify the receptor CXCR4 within the module and its ligand CXCL12 expressed in the graft as a likely recruitment mechanism between circulating cells and the tissue. We then explore publicly available transcriptomics data in circulating cells and show that this module is generally expressed in healthy individuals and more importantly is associated with the response to infection, including SARS Covid-19. Moreover, we find that module expression is predictive of immune mediated diseases. In summary, we find a gene expression module in circulating immune cells which enables preferential recruitment to inflamed tissues to mediate effector function.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.11.536347v1" target="_blank">A gene-expression module in circulating immune cells is associated with cell migration during immune diseases.</a>
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</div></li>
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<li><strong>A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples</strong> -
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The extent to which dengue virus has been circulating in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection; the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform a dengue seroprevalence survey which is currently being conducted in Ghana by the Drug for Neglected disease initiative, utilizing samples previously collected fora SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288282v1" target="_blank">A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples</a>
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<li><strong>Development of Accurate Long-lead COVID-19 Forecast</strong> -
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Coronavirus disease 2019 (COVID-19) will likely remain a major public health burden; accurate forecast of COVID-19 epidemic outcomes several months into the future is needed to support more proactive planning. Here, we propose strategies to address three major forecast challenges, i.e., error growth, the emergence of new variants, and infection seasonality. Using these strategies in combination we generate retrospective predictions of COVID-19 cases and deaths 6 months in the future for 10 representative US states. Tallied over >25,000 retrospective predictions through September 2022, the forecast approach using all three strategies consistently outperformed a baseline forecast approach without these strategies across different variant waves and locations, for all forecast targets. Overall, probabilistic forecast accuracy improved by 64% and 38% and point prediction accuracy by 133% and 87% for cases and deaths, respectively. Real-time 6-month lead predictions made in early October 2022 suggested large attack rates in most states but a lower burden of deaths than previous waves during October 2022 - March 2023; these predictions are in general accurate compared to reported data. The superior skill of the forecast methods developed here demonstrate means for generating more accurate long-lead forecast of COVID-19 and possibly other infectious diseases.
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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/10.1101/2022.11.14.22282323v2" target="_blank">Development of Accurate Long-lead COVID-19 Forecast</a>
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</div></li>
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<li><strong>A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Vaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.
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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/10.1101/2023.04.11.23288409v2" target="_blank">A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</a>
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<li><strong>Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination</strong> -
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Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to excipient polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Methods: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020 - March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination (“controls”) were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay. Anti-PEG IgG and IgM were measured using two different assays. Laboratorians were blinded to case/control status. Results: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65%) were hospitalized and 7 (35%) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10%) case-patients vs 8 of 30 (27%) controls (p=0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0%) vs 1 of 30 (3%) controls (p>0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Conclusion: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.11.23288372v1" target="_blank">Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination</a>
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<li><strong>Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in patients with and without long COVID</strong> -
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Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection provokes autoantibody responses and whether vaccination can decrease these responses in long COVID patients is unknown. Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than convalescent controls at more than 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination does not decrease autoantibody titers. In summary, we found that mild SARS-CoV-2 infection can induce long-term humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288243v1" target="_blank">Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in patients with and without long COVID</a>
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<li><strong>An Azapeptide Platform in Conjunction with Covalent Warheads to Uncover High-Potency Inhibitors for SARS-CoV-2 Main Protease</strong> -
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Main protease (MPro) of SARS-CoV-2, the viral pathogen of COVID-19, is a crucial nonstructural protein that plays a vital role in the replication and pathogenesis of the virus. Its protease function relies on three active site pockets to recognize P1, P2, and P4 amino acid residues in a substrate and a catalytic cysteine residue for catalysis. By converting the P1 C(alpha) atom in an MPro substrate to nitrogen, we showed that a large variety of azapeptide inhibitors with covalent warheads targeting the MPro catalytic cysteine could be easily synthesized. Through the characterization of these inhibitors, we identified several highly potent MPro inhibitors. Specifically, one inhibitor, MPI89 that contained an aza-2,2-dichloroacetyl warhead, displayed a 10 nM EC50 value in inhibiting SARS-CoV-2 from infecting ACE2+ A549 cells and a selectivity index of 875. The crystallography analyses of MPro bound with 6 inhibitors, including MPI89, revealed that inhibitors used their covalent warheads to covalently engage the catalytic cysteine and the aza-amide carbonyl oxygen to bind to the oxyanion hole. MPI89 represents one of the most potent MPro inhibitors developed so far, suggesting that further exploration of the azapeptide platform and the aza-2,2-dichloroacetyl warhead is needed for the development of potent inhibitors for the SARS-CoV-2 MPro as therapeutics for COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.11.536467v1" target="_blank">An Azapeptide Platform in Conjunction with Covalent Warheads to Uncover High-Potency Inhibitors for SARS-CoV-2 Main Protease</a>
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<li><strong>Analysis of SARS-CoV-2 Recombinant Lineages XBC and XBC.1 in the Philippines and Evidence for Delta-Omicron Co-infection as a Potential Origin</strong> -
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We report the sequencing and analysis of 60 XBC and 114 XBC.1 SARS-CoV-2 lineages detected in the Philippines from August to September 2022, which are regarded as recombinant lineages of the BA.2 Omicron and B.1.617.2 Delta (21I Clade) variants. The sequences described here place the Philippines as the country with the earliest and highest number of XBC and XBC.1 cases within the included period. Majority of the detected cases were sampled from the adjacent Davao and Soccskargen regions in southern Philippines, but have also been observed at lower proportions in other regions of the country. Time-scaled phylogenetic analysis with global samples from GISAID reaffirms the supposed root of XBC-like cases from the Philippines. Furthermore, the apparent clustering of some foreign cases separate from those collected in the country suggests several occurrences of cross-border transmissions resulting in the spread of XBC-like lineages within and among those countries. The consensus mutation profile shows regions harboring mutations specific to either the Omicron BA.2 or Delta B.1.617.2 lineages, supporting the recombinant nature of XBC. Finally, alternative allele fraction pattern and intrahost mutation analysis revealed that a relatively early case of XBC collected in March 2022 is likely to be an active co-infection event. This suggests that co-infection of Omicron and Delta was already occurring in the Philippines early in 2022, facilitating the generation of recombinants that may have further evolved and gained additional mutations enabling its spread across certain local populations at a later time.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.12.534029v1" target="_blank">Analysis of SARS-CoV-2 Recombinant Lineages XBC and XBC.1 in the Philippines and Evidence for Delta-Omicron Co-infection as a Potential Origin</a>
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<li><strong>Learning from pre-pandemic data to forecast viral escape</strong> -
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Effective pandemic preparedness relies on anticipating viral mutations that are able to evade host immune responses in order to facilitate vaccine and therapeutic design. However, current strategies for viral evolution prediction are not available early in a pandemic - experimental approaches require host polyclonal antibodies to test against and existing computational methods draw heavily from current strain prevalence to make reliable predictions of variants of concern. To address this, we developed EVEscape, a generalizable, modular framework that combines fitness predictions from a deep learning model of historical sequences with biophysical structural information. EVEscape quantifies the viral escape potential of mutations at scale and has the advantage of being applicable before surveillance sequencing, experimental scans, or 3D structures of antibody complexes are available. We demonstrate that EVEscape, trained on sequences available prior to 2020, is as accurate as high-throughput experimental scans at anticipating pandemic variation for SARS-CoV-2 and is generalizable to other viruses including Influenza, HIV, and understudied viruses with pandemic potential such as Lassa and Nipah. We provide continually updated escape scores for all current strains of SARS-CoV-2 and predict likely additional mutations to forecast emerging strains as a tool for ongoing vaccine development (evescape.org).
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.21.501023v2" target="_blank">Learning from pre-pandemic data to forecast viral escape</a>
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<li><strong>Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged ≥50 years in Ontario, Canada</strong> -
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Objective: We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Methods: We used a test-negative design to estimate vaccine effectiveness (VE), with unvaccinated adults as the comparator, against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years between June 19, 2022 and January 28, 2023 stratified by time since vaccination. We explored VE by vaccine product (Moderna Spikevax ® monovalent; Pfizer-BioNTech Comirnaty® monovalent; Moderna Spikevax® BA.1 bivalent; Pfizer-BioNTech Comirnaty® BA.4/BA.5 bivalent). Results: We included 3,755 Omicron cases and 14,338 test-negative controls. For the Moderna and Pfizer-BioNTech monovalent vaccines, VE 7-29 days after vaccination was 85% (95% confidence interval [CI], 72-92%) and 88% (95%CI, 82-92%), respectively, and was 82% (95%CI, 76-87%) and 82% (95%CI, 77-86%) 90-119 days after vaccination. For the Moderna BA.1 bivalent vaccine, VE was 86% (95%CI, 82-90%) 7-29 days after vaccination and was 76% (95%CI, 66-83%) 90-119 days after vaccination. For the Pfizer-BioNTech BA.4/BA.5 bivalent vaccine, VE 7-29 days after vaccination was 83% (95%CI, 77-88%) and was 81% (95%CI 72-87%) 60-89 days after vaccination. Conclusions: Booster doses of monovalent and bivalent mRNA COVID-19 vaccines provided similar, strong initial protection against severe outcomes in community-dwelling adults aged ≥50 years in Ontario. Nonetheless, uncertainty remains around waning protection of these vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.11.23288403v1" target="_blank">Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged ≥50 years in Ontario, Canada</a>
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<li><strong>The landscape of biomedical research</strong> -
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The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D atlas of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We base our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we use a large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We use our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, and the distribution of gender imbalance in academic authorship. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.10.536208v1" target="_blank">The landscape of biomedical research</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Standard of Care + Quinine Sulfate; Drug: Standard of Care<br/><b>Sponsors</b>: Universitas Padjadjaran; National Research and Innovation Agency of Indonesia; Prodia Diacro Laboratories P.T.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Biological: MSC-derived exosomes<br/><b>Sponsor</b>: Huazhong University of Science and Technology<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 Nasal Treatment for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Optate; Drug: Placebo<br/><b>Sponsor</b>: Indiana University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ropeginterferon alfa-2b; Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>: COVID19 Testing<br/><b>Interventions</b>: Behavioral: FABI tailored COVID-19 testing pamphlet; Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>: Texas Woman’s 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>Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual<br/><b>Sponsor</b>: Universität Duisburg-Essen<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 Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: PF-07817883; Drug: Placebo<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>: China-Japan Friendship 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>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>: COVID-19; Diagnostic Test<br/><b>Intervention</b>: Device: Lollipop<br/><b>Sponsor</b>: University of Wisconsin, Madison<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>Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination</strong> - <b>Conditions</b>: Vaccine Refusal; COVID-19<br/><b>Interventions</b>: Behavioral: Informational Video; Behavioral: Altruistic Video; Behavioral: Individualistic Video<br/><b>Sponsor</b>: Sir Mortimer B. Davis - Jewish General Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Interventions</b>: Drug: Testofen; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: RDC Clinical Pty 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>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>: Healthy; COVID-19; Distress, Emotional<br/><b>Interventions</b>: Behavioral: RASMUS Resilience Training; Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>: Medical University Innsbruck<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rehabilitation Treatment of Patients With COVID-19</strong> - <b>Conditions</b>: Rehabilitation; Pneumonia, Viral; COVID-19; Quality of Life<br/><b>Interventions</b>: Other: exercises; Other: massage<br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University; MEDSI Clinical Hospital 1, ICU<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Addressing Vaccine Acceptance in Carceral Settings Through Community Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: ADVANCE Steering Committee interventions<br/><b>Sponsors</b>: Yale University; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>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>Low Peripheral B-Cell Counts in Patients With Systemic Rheumatic Diseases Due to Treatment With Belimumab and/or Rituximab Are Associated With Low Antibody Responses to Primary COVID-19 Vaccination</strong> - Background: Immunosuppressive agents inhibit COVID-19 vaccine antibody (Ab) responses in patients with systemic rheumatic diseases. Rituximab may fully block Ab responses when B cells become undetected. The effect of detected but low number of B cells due to treatment with a B-cell agent (belimumab and/or rituximab) has not been established. Purpose: We sought to examine whether there is an association between a low number of B cells due to treatment with belimumab and/or rituximab and impaired…</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>Impulsive Neural Control to Schedule Antivirals and Immunomodulators for COVID-19</strong> - New SARS-CoV-2 variants escaping the effect of vaccines are an eminent threat. The use of antivirals to inhibit the viral replication cycle or immunomodulators to regulate host immune responses can help to tackle the viral infection at the host level. To evaluate the potential use of these therapies, we propose the application of an inverse optimal neural controller to a mathematical model that represents SARS-CoV-2 dynamics in the host. Antiviral effects and immune responses are considered as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 Activity of <em>Ampelozizyphus amazonicus</em> (Saracura-Mirá): Focus on the Modulation of the Spike-ACE2 Interaction by Chemically Characterized Bark Extracts by LC-DAD-APCI-MS/MS</strong> - Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents. Ampelozizyphus amazonicus is popularly used in the Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of A. amazonicus, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful…</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>Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application</strong> - The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of Papaver somniferum L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine…</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>Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19: A Computational Molecular Docking and Dynamic Simulation Approach</strong> - Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring the Potential Medicinal Benefits of <em>Ganoderma lucidum</em>: From Metabolic Disorders to Coronavirus Infections</strong> - Ganoderma lucidum is a medicinal mushroom that has been traditionally used in Chinese medicine for centuries. It has been found to have a wide range of medicinal properties, including antioxidant, anti-inflammatory, and immune-boosting effects. Recent research has focused on the potential benefits of G. lucidum in treating metabolic disorders such as diabetes and obesity, as well as its possible role in preventing and treating infections caused by the coronavirus. Triterpenoids are a major group…</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 Signaling Pathway of the ADP Receptor P2Y<sub>12</sub> in the Immune System: Recent Discoveries and New Challenges</strong> - P2Y(12) is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y(12) has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y(12) is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, 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>COVID-19 and Diarylamidines: The Parasitic Connection</strong> - As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of “post-COVID-19 syndrome” and associated…</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>Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection</strong> - The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3’ to 5’ exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations</strong> - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents….</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>Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir</strong> - The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site. Individual monomers, however, have very low or…</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>Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions</strong> - Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general…</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>Broad-spectrum coronavirus 3C-like protease peptidomimetic inhibitors effectively block SARS-CoV-2 replication in cells: Design, synthesis, biological evaluation, and X-ray structure determination</strong> - Despite the approval of vaccines, monoclonal antibodies and restrictions during the pandemic, the demand for new efficacious and safe antivirals is compelling to boost the therapeutic arsenal against the COVID-19. The viral 3-chymotrypsin-like protease (3CL^(pro)) is an essential enzyme for replication with high homology in the active site across CoVs and variants showing an almost unique specificity for Leu-Gln as P2-P1 residues, allowing the development of broad-spectrum inhibitors. 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>Modulation of <em>in Vitro</em> SARS-CoV-2 Infection by <em>Stephania tetrandra</em> and Its Alkaloid Constituents</strong> - Botanical natural products have been widely consumed for their purported usefulness against COVID-19. Here, six botanical species from multiple sources and 173 isolated natural product compounds were screened for blockade of wild-type (WT) SARS-CoV-2 infection in human 293T epithelial cells overexpressing ACE-2 and TMPRSS2 protease (293TAT). Antiviral activity was demonstrated by an extract from Stephania tetrandra. Extract fractionation, liquid chromatography-mass spectrometry (LC-MS),…</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 drug-drug interactions of ensitrelvir, a SARS-CoV-2 3CL protease inhibitor, with transporter substrates based on in vitro and a clinical study</strong> - Drug-drug interaction (DDI) potentials of ensitrelvir, a novel oral inhibitor of 3C-like protease of SARS-CoV-2, for drug transporters were evaluated by in vitro and clinical studies. The target drug transporters assessed were P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion (MATE) 1 and MATE-2K. In vitro study…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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