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<title>09 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>A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</strong> -
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<div>
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Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e., Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-{beta}, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.05.535806v1" target="_blank">A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</a>
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</div></li>
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<li><strong>The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</strong> -
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Biomolecular condensates (BMCs) play important roles in cellular structures including transcription factories, splicing speckles, and nucleoli. BMCs bring together proteins and other macromolecules, selectively concentrating them so that specific reactions can occur without interference from the surrounding environment. BMCs are often made up of proteins that contain intrinsically disordered regions (IDRs), form phase-separated spherical puncta, form liquid-like droplets that undergo fusion and fission, contain molecules that are mobile, and are disrupted with phase-dissolving drugs such as 1,6-hexanediol. In addition to cellular proteins, many viruses, including influenza A, SARS-CoV-2, and human immunodeficiency virus type 1 (HIV-1) encode proteins that undergo phase separation and rely on BMC formation for replication. In prior studies of the retrovirus Rous sarcoma virus (RSV), we observed that the Gag protein forms discrete spherical puncta in the nucleus, cytoplasm, and at the plasma membrane that co-localize with viral RNA and host factors, raising the possibility that RSV Gag forms BMCs that participate in the virion intracellular assembly pathway. In our current studies, we found that Gag contains IDRs in the N-terminal (MAp2p10) and C-terminal (NC) regions of the protein and fulfills many criteria of BMCs. Although the role of BMC formation in RSV assembly requires further study, our results suggest the biophysical properties of condensates are required for the formation of Gag complexes in the nucleus and the cohesion of these complexes as they traffic through the nuclear pore, into the cytoplasm, and to the plasma membrane, where the final assembly and release of virus particles occurs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.07.536043v1" target="_blank">The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</a>
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<li><strong>GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</strong> -
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Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targets in vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils’ yield, purity, functionality, and maturity through the deletion of the transcription factor GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, through CRSPR/Cas9 deletion of CYBB we demonstrate that GATA1 KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.526339v3" target="_blank">GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</a>
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<li><strong>A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</strong> -
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Early detection of infection with SARS-CoV-2 is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosis of SARS-CoV-2 infection, dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), that enhances sensitivity by aiming to amplify the entire SARS-CoV-2 genome rather than targeting particular viral loci, as in typical RT-PCR assays. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. We are able to reliably (>95% accuracy) detect SARS-CoV-2 at concentrations of 84 genome equivalents per milliliter, better than the reported limits of detection of almost all diagnostic methods currently approved by the US Food and Drug Administration. At higher concentrations, we are able to reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy. Such genome assemblies enable the spread of the disease to be analyzed much more effectively than would be possible with an ordinary yes/no diagnostic, and can help identify vaccine and drug targets. Finally, we show that POLAR diagnoses on 10 of 10 clinical nasopharyngeal swab samples (half positive, half negative) match those obtained in a CLIA-certified lab using the Center for Disease Control’s 2019-Novel Coronavirus test. Using POLAR, a single person can process 192 samples over the course of an 8-hour experiment, at a cost of ~$30/patient, enabling a 24-hour turnaround with sequencing and data analysis time included. Further testing and refinement will likely enable greater enhancements in the sensitivity of the above approach.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.04.25.061499v4" target="_blank">A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</a>
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<li><strong>The effect of perceived morbidity and mortality risk on risk-taking and patience</strong> -
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Beyond immediate health consequences, the COVID-19 pandemic has profoundly affected people’s environment. People had to adapt to new circumstances and take into account the risks related to COVID-19 in their everyday decisions. Given the unprecedented circumstances associated with the first wave of the COVID-19 pandemic, we might ask how people adapt to their new environment. In particular, we ask how people form their morbidity and mortality risk perception associated with the virus and whether increased perceived risk affects psychological traits, such as risk-taking and patience. To address these questions, we analyzed data from a large survey conducted during the first wave in France on 5,000 nationally-representative people. We find that people use the public information on COVID-19 deaths in the area where they live to form their perceived morbidity and mortality risk. Using a structural model approach to lift endogeneity concerns, we found that higher perceived morbidity and mortality risk increases risk aversion. We also found that higher perceived morbidity and mortality risk leads to less patience, although this was only observed for high levels of perceived risk.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/u768y/" target="_blank">The effect of perceived morbidity and mortality risk on risk-taking and patience</a>
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<li><strong>Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background:The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Recently, self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. Methods:This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Close contacts will be randomized to either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. Discussion:This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure.
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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/10.1101/2023.04.05.23288207v1" target="_blank">Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</a>
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<li><strong>The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</strong> -
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Coronaviridae is recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections, as well as enteric and neurological diseases. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50 ranging between 0.05 and 0.15 g/ml and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.13.499346v2" target="_blank">The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</a>
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<li><strong>The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</strong> -
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The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N-glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N-glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody binding. Glycan site-occupancy analyses revealed that the mutation resulted in N-glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535004v1" target="_blank">The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</a>
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<li><strong>Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</strong> -
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The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5{+/-}72.3, p<0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 units. Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535504v1" target="_blank">Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</a>
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<li><strong>Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</strong> -
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Importance Investigating the role of pre–infection humoral immunity against Omicron BA.5 infection risk and long COVID development is critical to inform public health guidance. Objective To investigate the association between pre–infection immunogenicity after the third vaccine dose and the risks of Omicron BA.5 infection and long coronavirus disease. Design, Setting, and Participants This nested case–control analysis was conducted among tertiary hospital staff in Tokyo, Japan who donated blood samples in June 2022 (1 month before Omicron BA.5 dominant wave onset [July–September 2022]) approximately 6 months after receiving the third dose of the historical monovalent coronavirus disease 2019 mRNA vaccine. Exposures Live virus–neutralizing antibody titers against Wuhan and Omicron BA.5 (NT50) and anti–SARS–CoV–2 spike protein antibody titers with Abbott (AU/mL) and Roche (U/mL) assays at pre–infection. Main Outcomes and Measures Symptomatic SARS–CoV–2 breakthrough infections during the Omicron BA.5 dominant wave vs. undiagnosed controls matched using a propensity score. Incidence of long COVID (persistent symptoms ≥4 weeks after infection) among breakthrough infection cases. Results Anti–spike antibody titers were compared between 243 breakthrough infection cases and their matched controls among the 2360 staff members who met the criteria. Neutralizing antibodies in 50 randomly selected matched pairs were measured and compared. Pre–infection anti-spike and neutralizing antibody titers were lower in breakthrough cases than in undiagnosed controls. Neutralizing antibody titers against Wuhan and Omicron BA.5 were 64% (95% CI: 42–77) and 72% (95% CI: 53–83) lower, respectively, in breakthrough cases than in undiagnosed controls. Individuals with previous SARS-CoV-2 infections were more frequent among undiagnosed controls than breakthrough cases (19.3% vs. 4.1%), and their neutralizing antibody titers were higher than those of infection–naive individuals. Among the breakthrough cases, pre–infection antibody titers were not associated with the incidence of long COVID. Conclusions and Relevance Pre–infection immunogenicity against SARS–CoV–2 may play a role in protecting against the Omicron BA.5 infection, but not in preventing long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288162v1" target="_blank">Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</a>
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<li><strong>Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</strong> -
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Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response following vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) versus BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed for randomized and observational studies using the Risk of Bias 2 tool and the Newcastle-Ottawa Scale, respectively. Evidence was evaluated using the GRADE framework. Results: Overall, 22 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR 0.87, 95% CI 0.79-0.96; P=0.0054; I2=61.9%), COVID-19-associated hospitalization (RR 0.83, 95% CI 0.76-0.90; P<0.0001; I2=0%), and COVID-19-associated mortality (RR 0.62, 95% CI 0.43-0.89; P=0.011; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials and evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288195v1" target="_blank">Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</a>
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<li><strong>Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir</strong> -
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Background: The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC. Methods: We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients ≥18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection. Results 1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p<0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days. Conclusions NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288196v1" target="_blank">Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir </a>
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<li><strong>Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</strong> -
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Background During the pandemic period, healthcare systems were substantially reorganized for managing COVID-19 cases. The corresponding changes on the standard care of persons with chronic diseases and the potential consequences on their outcomes remain insufficiently documented. This observational study investigates the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR), in particular in those not hospitalized for COVID-19. Methods We conducted a cohort study using the French national health data system which contains all healthcare consumptions in France. Incident persons with end stage kidney disease between January 1, 2015 and December 31, 2020 who received a kidney transplant were included and followed-up from their transplantation date to December 31, 2021. The survival of KTR during the pre-pandemic and pandemic periods was investigated using Cox models with time-dependent covariates, including vaccination and hospitalization events. Findings There were 10,637 KTR included in the study, with 324 and 430 deaths observed during the pre-pandemic (15,115 person-years of follow-up) and pandemic periods (14,657 person-years of follow-up), including 127 deaths observed among the 659 persons with a COVID-19-related hospitalization. In multivariable analyses, the risk of death during the pandemic period was similar to that observed during the pre-pandemic period (hazard ratio (HR) [95% confidence interval]: 0.92 [0.77-1.11]), while COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]). In addition, pre-emptive kidney transplantation was associated with a lower risk of death (HR: 0.71 [0.56-0.89]), as well as a third vaccine dose (HR: 0.42 [0.30-0.57]), while age, diabetes and cardiovascular diseases were associated with higher risks of death. Interpretation Considering persons living with a kidney transplant with no severe COVID-19-related hospitalization, the pandemic period was not associated with a higher risk of death.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288113v1" target="_blank">Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</a>
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<li><strong>Second-order Citations in Altmetrics: A Case Study Analyzing the Audiences of COVID-19 Research in the News and on Social Media</strong> -
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The potential to capture the societal impact of research has been a driving motivation for the use and development of altmetrics. Yet, to date, altmetrics have largely failed to deliver on this potential because the primary audience who cites research on social media has been shown to be academics themselves. In response, our study investigates an extension of traditional altmetric approaches that goes beyond capturing direct mentions of research on social media. Using research articles from the first months of the COVID-19 pandemic as a case study, we demonstrate the value of measuring ‘second-order citations,’ or social media mentions of news coverage of research. We find that a sample of these citations, published by just five media outlets, were shared and engaged with on social media twice as much as the research articles themselves. Moreover, first-order and second-order citations circulated among Twitter accounts and Facebook accounts that were largely distinct from each other. The differences in audiences and engagement patterns found in this case study highlight the importance of news coverage as a public source of science information and provide strong evidence that investigating these second-order citations can be an effective way of observing non-academic audiences that engage with research content.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.05.535734v1" target="_blank">Second-order Citations in Altmetrics: A Case Study Analyzing the Audiences of COVID-19 Research in the News and on Social Media</a>
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<li><strong>Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant</strong> -
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At the end of March 2023, XBB.1.16, a SARS-CoV-2 omicron XBB subvariant, emerged and was detected in various countries. Compared to XBB.1.5, XBB.1.16 has two substitutions in the S protein: E180V is in the N-terminal domain, and T478K in the receptor-binding domain (RBD). We first show that XBB.1.16 had an effective reproductive number (Re) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5, respectively, suggesting that XBB.1.16 will spread worldwide in the near future. In fact, the WHO classified XBB.1.16 as a variant under monitoring on March 30, 2023. Neutralization assays demonstrated the robust resistance of XBB.1.16 to breakthrough infection sera of BA.2 (18-fold versus B.1.1) and BA.5 (37-fold versus B.1.1). We then used six clinically-available monoclonal antibodies and showed that only sotrovimab exhibits antiviral activity against XBB subvariants, including XBB.1.16. Our results suggest that, similar to XBB.1 and XBB.1.5, XBB.1.16 is robustly resistant to a variety of anti-SARS-CoV-2 antibodies. Our multiscale investigations suggest that XBB.1.16 that XBB.1.16 has a greater growth advantage in the human population compared to XBB.1 and XBB.1.5, while the ability of XBB.1.16 to exhibit profound immune evasion is comparable to XBB.1 and XBB.1.5. The increased fitness of XBB.1.16 may be due to (1) different antigenicity than XBB.1.5; and/or (2) the mutations in the non-S viral protein(s) that may contribute to increased viral growth efficiency.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.06.535883v1" target="_blank">Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant</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 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>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: usual care and follow-up by a nurse; Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de Saint Etienne<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Chinese Herb; Diagnostic Test: Placebo<br/><b>Sponsor</b>: Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsors</b>: First Affiliated Hospital of Wenzhou Medical University; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<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>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: NP-101; Other: Placebo<br/><b>Sponsor</b>: Novatek Pharmaceuticals<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>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>Care for Veterans Post-COVID</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Concordant Care Training; Behavioral: Education Packet Training<br/><b>Sponsor</b>: VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Complementary Self-help Strategies for Patients With Post-COVID 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>Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals</strong> - <b>Conditions</b>: Infectious Disease; COVID-19<br/><b>Interventions</b>: Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration<br/><b>Sponsor</b>: RVAC Medicines (US), Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 Nasal Spray; Drug: Placebo<br/><b>Sponsor</b>: Huahui Health<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions</strong> - SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant…</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>Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection</strong> - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of a Peptide Sensor Derived from Human ACE2 for Fluorescence Polarization Assays of the SARS-CoV-2 Receptor Binding Domain</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuing emergence of infectious variants have caused a serious pandemic and a global economic slump since 2019. To overcome the situation and prepare for future pandemic-prone diseases, there is a need to establish a convenient diagnostic test that is quickly adaptable to unexpected emergence of virus variants. Here we report a fluorescent peptide sensor 26-Dan and its application to the fluorescence polarization (FP) assay…</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 a rapid fluorescence immunochromatographic test with an enzyme-linked immunosorbent assay for measurement of SARS-CoV-2 spike protein antibody neutralizing activity</strong> - CONCLUSION: FIC had good qualitative agreement with ELISA in the detection of positive NAbs-RBD(%) and could be an alternative for rapid NAbs-RBD(%) testing.</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 antibody response to coronavirus disease 2019 vaccination between patients with solid or hematologic cancer patients undergoing chemotherapy</strong> - CONCLUSION: Hematologic cancer patients receiving chemotherapy tended to respond poorly to both COVID-19 mRNA and vector vaccines and had a significantly lower antibody titer compared to those with solid cancers.</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 covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication</strong> - Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro,…</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>Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection</strong> - Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation…</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>TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled trial</strong> - CONCLUSIONS: TRPC6 inhibition was not effective in reducing the risk and/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.</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 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection</strong> - Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemical Composition of Honeysuckle (<em>Lonicerae japonicae</em>) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals</strong> - Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both…</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>Surfactin-like lipopeptides from <em>Bacillus clausii</em> efficiently bind to spike glycoprotein of SARS-CoV-2</strong> - The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic…</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 immune boosting and anti-viral efficacy of <em>Parkia</em> bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods</strong> - The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Attitudes and concerns regarding booster dose of COVID-19 vaccine among Egyptian patients with autoimmune and rheumatic diseases: a cross-sectional survey study</strong> - CONCLUSIONS: There is a low acceptability rate of booster dose of COVID-19 vaccine among Egyptian patients with ARD diseases. Public health workers and policymakers need to make sure that all ARD patients get clear messages about accepting the COVID-19 booster dose.</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 (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?</strong> - Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19</strong> - CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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