Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• SARS-CoV-2 Delta Variant Remains Viable in Environmental Biofilms found in Meat Packaging Plants -
  To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81 - 4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants.
  🖺 Full Text HTML: SARS-CoV-2 Delta Variant Remains Viable in Environmental Biofilms found in Meat Packaging Plants
• High-confidence placement of difficult-to-fit fragments into electron density by using anomalous signals - a case study using hits targeting SARS-CoV-2 non-structural protein 1 -
  The identification of multiple simultaneous orientations of small molecule inhibitors binding to a protein target is a common challenge. It has recently been reported that the conformational heterogeneity of ligands is widely underreported in the Protein Data Bank, which is likely to impede optimal exploitation to improve affinity of these ligands. Significantly less is even known about multiple binding orientations for fragments (< 300 Da) although this information would be essential for subsequent fragment optimisation using growing, linking or merging and rational structure-based design. Here we use recently reported fragment hits for the SARS-CoV-2 non-structural protein 1 (nsp1) N-terminal domain to propose a general procedure for unambiguously identifying binding orientations of 2-dimensional fragments containing either sulphur or chloro substituents within the wavelength range of most tunable beamlines. By measuring datasets at two energies, using a tuneable beamline operating in vacuum and optimised for data collection at very low X-ray energies, we show that the anomalous signal can be used to identify multiple orientations in small fragments containing sulphur and/or chloro substituents or to verify recently reported conformations. Although in this specific case we identified the positions of sulphur and chlorine in fragments bound to their protein target, we are confident that this work can be further expanded to additional atoms or ions which often occur in fragments. Finally, our improvements in the understanding of binding orientations will also serve to improve the rational optimisation of SARS-CoV-2 nsp1 targeting fragment hits.
  🖺 Full Text HTML: High-confidence placement of difficult-to-fit fragments into electron density by using anomalous signals - a case study using hits targeting SARS-CoV-2 non-structural protein 1
• Evaluation of 3-D printed swabs for respiratory sampling and testing for SARS-CoV-2 during the early pandemic period -

  Appropriate collection of respiratory samples is essential for accurate diagnostic testing of respiratory pathogens such as, SARS-CoV-2. Early in the pandemic, there was a shortage of nasopharyngeal (NP) swabs and difficulty in sampling suspected cases. Therefore, we developed a 3D printed nasal swab for anterior nares, paired with in-house viral transport medium (VTM). The utility of this 3D swab kit was investigated in comparison with the standard NP commercial swab and VTM, in 200 individuals between August and September 2021. Subjects were those presenting for diagnostic testing for SARS-CoV-2 using the RT- PCR (cobas Roche assay) assay. NP samples were taken from each subject using the standard NP and 3D swabs followed by RT-PCR on paired specimens. CT values for amplification of gene targets were evaluated to determine assay parameters based on viral load cut offs of ≤ CT 35 or, ≤ CT 37. For high to medium viral loads, 3D swab based PCR testing had a sensitivity of 93%, specificity of 99%, positive predictive value (PPV) of 98.5% and negative predictive value (NPV) of 96.2% respectively. For low viral loads, 3D swab testing had a sensitivity of 88%, specificity of 99%, with a PPV of 98.5% and NPV of 93.2%.%. 3D swab sampling of anterior nares was comparable with NP sampling using standard swabs for SARS-CoV-2 specimens with a medium to high viral load. Therefore, 3D swab based sampling is a reliable and convenient local solution for collecting respiratory samples for SARS-CoV-2 diagnostic testing.

  🖺 Full Text HTML: Evaluation of 3-D printed swabs for respiratory sampling and testing for SARS-CoV-2 during the early pandemic period
• Determinants of post-acute COVID-19 syndrome among hospitalized severe COVID-19 patients: a 2-year follow-up study -

  Abstract Background: Coronavirus disease–19 (COVID–19), emerged as a public health threat in December 2019. The number of COVID–19 cases worldwide is now more than 765 million with more than 6.9 million dead. During follow–up visits following discharge, a large percentage of patients were discovered to still be suffering from health issues that lower their quality of life and ability to return to work. This study assessed the prevalence and associated risk factors of post-acute COVID–19 syndrome (PACS) among severe COVID–19 patients who were discharged from Millennium COVID–19 care center, Addis Ababa, Ethiopia. Methods: A cross–sectional study using data collected from patient charts and a follow–up telephone interview after two years of discharge. Systematic random sampling was used to select a total of 400 patients. A structured questionnaire developed from the case report form for PACS of WHO was used. Frequency and cross–tabulation were used for descriptive statistics. Predictor variables with a p–value <0.25 in bivariate analyses were included in the logistic regression. Result: Out of the 400 patients, 20 patients were dead, 14 patients refused to give consent, and 26 patients could not be reached because their phone was not working. Finally, 340 were included in the study. The majority (68.5%) were males and the mean age was 53.9 (±13.3 SD) years. Most of the patients (60%) has one or more comorbidity. The most common symptom at presentation was cough (93.5%), followed by shortness of breath (82.1%) and fatigue (69.7%). The mean duration of hospital admission was 12.3 (±6.5 SD) days. More than a third (38.1%) of the patients reported the persistence of at least one symptom after hospital discharge. The most common symptoms were fatigue (27.5%) and Cough (15.3%). older age (AOR 1.04, 95% CI 1.02 – 1.07), female sex (AOR 1.82, 95% CI 1.00 – 3.29), presence of comorbidity (AOR 2.38, 95% CI 1.35 – 4.19), alcohol use (AOR 3.05, 95% CI 1.49 – 6.26), fatigue at presentation (AOR 2.18, 95% CI 1.21 – 3.95), and longer hospital stay (AOR 1.06, 95% CI 1.02 – 1.10) were foundto increase the odds of developing post–acute COVID-19 syndrome. Higher hemoglobin level was found to decrease the risk of subsequent post–acute COVID–19 syndrome (AOR 0.84, 95% CI 0.71 – 0.99). Conclusion: establishing a dedicated PACS followup clinic, especially for those with a higher risk can help to provide comprehensive care for the patients and improve their quality of life. Keywords: Post –acute COVID –19 syndrome, Long COVID, Chronic COVID –19

  🖺 Full Text HTML: Determinants of post-acute COVID-19 syndrome among hospitalized severe COVID-19 patients: a 2-year follow-up study
• Omicron vs. the Rest: Assessing the Competitive Dynamics and Coinfection Scenarios of COVID-19 Strains on a Social Network -

  The rapid spread and evolving nature of COVID-19 variants have raised concerns regarding their competitive dynamics and coinfection scenarios. In this study, we assess the competitive interactions between the Omicron variant and other prominent variants (Alpha, Beta, and Delta) on a social network, considering both single infection and coinfection states. Using the SIRS model, we simulate the progression of these variants and analyze their impact on infection rates, mortality, and overall disease burden. Our findings demonstrate that the Alpha and Beta strains exhibit comparable contagion levels, with the Alpha strain displaying higher infection and mortality rates. Moreover, the Delta strain emerges as the most prevalent and virulent strain, surpassing the other variants. When introduced alongside the less virulent Omicron strain, the Delta strain results in higher infection and mortality rates. However, the Omicron strain9s dominance leads to an overall increase in disease statistics. Remarkably, our study highlights the efficacy of the Omicron variant in supplanting more virulent strains and its potential role in mitigating the spread of infectious diseases. The Omicron strain demonstrates a competitive advantage over the other variants, suggesting its potential to reduce the severity of the disease and alleviate the burden on healthcare systems. These findings underscore the importance of monitoring and understanding the dynamics of COVID-19 variants, as they can inform effective prevention and mitigation strategies, particularly with the emergence of variants that possess a relative advantage in controlling disease transmission.

  🖺 Full Text HTML: Omicron vs. the Rest: Assessing the Competitive Dynamics and Coinfection Scenarios of COVID-19 Strains on a Social Network
• The relative effectiveness of a high-dose quadrivalent influenza vaccine vs standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-22 influenza season -

  Background: High-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/22 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccines (SD-QIV). This is the first study to estimate the relative vaccine effectiveness (rVE) of HD-QIV versus SD-QIV against influenza-related hospitalizations in France. Methods: Community-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/22 influenza season were included from the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the 5 previous years. Hospitalizations due to influenza and other causes were recorded from 14 days after vaccination to end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination and region. Incidence rate ratios (IRR) were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models. Results: We matched 405,385 (99.9%) HD-QIV to 1,621,540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95%CI: 8.4–35.8) lower rate of influenza hospitalizations compared to SD-QIV. Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and for negative control outcomes, suggesting residual confounding by indication. Conclusions: HD-QIV was associated with lower influenza-related hospitalization rates versus SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.

  🖺 Full Text HTML: The relative effectiveness of a high-dose quadrivalent influenza vaccine vs standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-22 influenza season
• Tracking SARS-CoV-2 seropositivity in rural communities using blood-fed mosquitoes -

  The spread of SARS-CoV-2 cannot be well monitored and understood in areas without capacity for effective disease surveillance. Countries with a young population will have disproportionately large numbers of asymptomatic or pauci-symptomatic infections, further hindering detection of infection in the population. Sero-surveillance on a country-wide scale by trained medical professionals may be limited in scope in resource limited setting such as Mali. Novel ways of broadly sampling the human population in a non-invasive method would allow for large-scale surveillance at a reduced cost. Here we evaluate the collection of naturally bloodfed mosquitoes to test for human anti-SARS-CoV-2 antibodies in the laboratory and at five field locations in Mali. Immunoglobulin-G antibodies were found to be readily detectable within the mosquito bloodmeals by a bead-based immunoassay at least through 10 hours post-feeding with high sensitivity (0.900 STD=0.059) and specificity (0.924 STD=0.080), respectively, indicating that most blood-fed mosquitoes collected indoors during early morning hours (and thus, have likely fed the previous night) are viable samples for analysis. We find that reactivity to four SARS-CoV-2 antigens rose during the pandemic from pre-pandemic levels. Consistent with other sero-surveillance studies in Mali, crude seropositivity of blood sampled via mosquitoes was 6.3% in October/November 2020 over all sites, and increased to 25.1% overall, with the town closest to Bamako reaching 46.7% in February of 2021. Mosquito bloodmeals a viable target for conventional immunoassays, and therefore country-wide sero-surveillance of human diseases (both vector-borne and non-vector-borne) is attainable in areas where human-biting mosquitoes are common, and is an informative, cost-effective, non-invasive sampling option.

  🖺 Full Text HTML: Tracking SARS-CoV-2 seropositivity in rural communities using blood-fed mosquitoes
• (PREPRINT PAPER) A Moderated Mediation Model of Self-Construal, Social Trust, and Compliance on Covid-19 Public Health Regulation: A Cross-country Analysis -
  To address the global Covid-19 pandemic, governments around the world require on the collective cooperation of their citizens to comply with public health regulation. Earlier studies examined the extent to which self-construal has an impact on individual compliance to law. However, existing literature has paid little significant attention to behavioural outcome of self-construal in the pandemic context across countries and cultures. The aim of this study was; 1) to determine whether interdependent self-construal predicts compliance of Covid-19 public health regulation, 2) to examine if the association was mediated by individual social trust, and 3) to test whether these associations were moderated by respondent’s country of residence (US x Indonesia). General adult respondents from US (N=231) and Indonesia (N=440) were voluntary participated in a survey measuring their trust to the government, interdependent self-construal orientation and compliance toward Covid-19 public health regulation. While our moderated mediation model involving respondent’s country residence did not support the hypothesis, the mediation analysis demonstrated significant association between interdependent self-construal and compliance via social trust. Our additional simple moderation analysis on direct effect of interdependent self-construal and compliance showed significant findings. Further, theoretical and practical implications of these findings were discussed in the following paper.
  🖺 Full Text HTML: (PREPRINT PAPER) A Moderated Mediation Model of Self-Construal, Social Trust, and Compliance on Covid-19 Public Health Regulation: A Cross-country Analysis
• M3NetFlow: a novel multi-scale multi-hop modular graph AI model for multi-omics data integration and signaling network inference -
  The integration and interpretation of multi-omics data play a crucial role in systems biology for prioritizing key molecular targets and deciphering core signaling pathways of complex diseases, such as cancer, covid-19 and Alzheimer's disease. However, it remains a challenge that has not been adequately addressed. Graph neural networks (GNN) have been emerged as powerful artificial intelligence models for analyzing data with a graphical structure. Nevertheless, GNN models have not been sufficiently designed for integrative and interpretable analysis of multi-omics data. In this study, we propose a novel multi-scale multi-hop modular GNN model, M3NetFlow, to integrate and interpret multi-omics data to rank key targets and infer core signaling pathways. Specifically, we applied the M3NetFlow model to infer cell-line specific core signaling networks explaining drug combination response. The evaluation and comparison results on drug combination prediction showed that the M3NetFlow model achieved significantly higher prediction accuracy than existing GNN models. Furthermore, M3NetFlow can predict key targets and infer essential signaling networks regulating drug combination response. It is critical for investigating mechanisms of synergy, and guiding the development of personalized precision medicine for patients with drug resistance. This model can be applied to general multi-omics data-driven research.
  🖺 Full Text HTML: M3NetFlow: a novel multi-scale multi-hop modular graph AI model for multi-omics data integration and signaling network inference
• Mapping SARS-CoV-2 antigenic relationships and serological responses -
  During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of human sera obtained following primary infection with 10 different variants or after mRNA-1273 or mRNA-1273.351 vaccination. We find antigenic differences among pre-Omicron variants caused by substitutions at spike protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months post-2nd dose. We find changes in immunodominance of different spike regions depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine strain selection.
  🖺 Full Text HTML: Mapping SARS-CoV-2 antigenic relationships and serological responses
• Perceptions Matter: Quasi-Experimental Evidence on the Effects of Spain’s New Minimum Income on Households’ Financial Wellbeing -
  This paper examines how minimum income schemes (MISs) affect households’ financial wellbeing and whether this effect differs across objective material conditions and households’ perceptions. Two reasons motivate this study. First, while the Covid-19 pandemic, the ecological transition and the cost-of-living crisis have all prompted a renewed interest in MISs, no consensus exists on how effective these schemes are in improving households’ financial wellbeing. Second, when evaluating MISs, the literature focuses on objective measures of financial wellbeing, namely monetary poverty. Yet, peoples’ perceptions of their own situation can be instrumental in affecting their health, productivity and decision-making and can reveal important information about adaptation mechanisms or spillovers to non-recipients. This paper examines the case study of Spain, a country that introduced a new MIS in 2020. The study uses Eurostat survey data for the 2010-2022 period in a Synthetic Control Method analysis. The results show that, while the policy had no significant effect on objective financial wellbeing measures (i.e. the poverty rate, the poverty gap and mean income) for its first year and a half of existence, it did considerably improve subjective financial wellbeing after two years and a half, as it helped households feel less pessimistic about the evolution of their finances during the Covid-19 and cost-of-living crises. The paper discusses several mechanisms explaining this differentiated impact of the policy, such as its lagged rollout, the improvements made to the benefit from 2022 as well as anticipation, placebo and positive spillover effects of the MIS. The findings highlight the importance for practitioners to consider subjective measures when assessing income support schemes.
  🖺 Full Text HTML: Perceptions Matter: Quasi-Experimental Evidence on the Effects of Spain’s New Minimum Income on Households’ Financial Wellbeing
• Measuring short-term mobility patterns in North America using Facebook Advertising data, with an application to adjusting Covid-19 mortality rates -
  Patterns and trends in short-term mobility are important to understand, but data required to measure such movements are often not available from traditional sources. We collected daily data from Facebook’s Advertising Platform to measure short-term mobility across all states and provinces in the United States and Canada. We show that rates of short-term travel vary substantially over geographic area, but also by age and sex, with the highest rates of travel generally for males. Strong seasonal patterns are apparent in travel to many areas, with different regions experiencing either increased travel or decreased travel over winter, depending on climate. Further, some areas appear to show marked changes in mobility patterns since the onset of the pandemic. We used the traveler rates constructed from Facebook to adjust Covid-19 mortality rates over the period July 2020 to July 2021, and showed that accounting for travelers leads to on average a 3 per cent difference in implied mortality rates, with substantial variation across demographic groups and regions.
  🖺 Full Text HTML: Measuring short-term mobility patterns in North America using Facebook Advertising data, with an application to adjusting Covid-19 mortality rates
• Are patterns of discounting choices stable over time? -
  Few studies have examined the stability of discounting responses over time. We examined delay and probabilistic discounting of losses at two time points, 13-16 months apart. We found that people do change over time in the frequency with which they select immediate and certain losses. These changes in discounting steepness for delayed and probabilistic losses were predicted by different profiles of state-dependent factors (i.e., local numbers of COVID-19 cases and deaths, anxiety, and depression). We also identified subgroups of individuals with different loss response patterns, and although the tendency to switch between subgroups over time was below chance, it was not negligible, particularly for delay discounting. Further, subgroup changes for delay, but not probabilistic, discounting were influenced by age as well as instability of income and intolerance of uncertainty. Together, these findings indicate the importance of considering temporal stability and the role of state-dependent factors in discounting research.
  🖺 Full Text HTML: Are patterns of discounting choices stable over time?
• Repurposing Remdesivir for COVID-19: Computational Drug Design Targeting SARS-CoV-2 RNA Polymerase and Main Protease using Molecular Dynamics Approach -
  The coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory illness that has become a global health crisis with new variants, an unprecedented number of infections, and deaths and demands urgent manufacturing of potent therapeutics. Despite the success of vaccination campaigns around the globe, there is no particular therapeutics approved to date for efficiently treating infected individuals. Repositioning or repurposing previously effective antivirals against RNA viruses to treat COVID-19 patients is a feasible option. Remdesivir is a broad-spectrum antiviral drug that the Food and Drug Administration (FDA) licenses for treating COVID-19 patients who are critically ill patients. Remdesivir's low efficacy, which has been shown in some clinical trials, possible adverse effects, and dose-related toxicities are issues with its use in clinical use. Our study aimed to design potent derivatives of remdesivir through the functional group modification of the parent drug targeting RNA-dependent RNA polymerase (RdRp) and main protease (MPro) of SARS-CoV-2. The efficacy and stability of the proposed derivatives were assessed by molecular docking and extended molecular dynamics simulation analyses. Furthermore, the pharmacokinetic activity was measured to ensure the safety and drug potential of the designed derivatives. The derivatives were non-carcinogenic, chemically reactive, highly interactive, and stable with the target proteins. D-CF3 is one of the designed derivatives that finally showed stronger interaction than the parent drug, according to the docking and dynamics simulation analyses, with both target proteins. However, in vitro and in vivo investigations are guaranteed to validate the findings in the future. Keywords: SARS-CoV-2; RNA-dependent RNA polymerase (RdRp); Main protease (MPro); Remdesivir; Modified derivatives; Molecular docking; Molecular dynamics simulation.
  🖺 Full Text HTML: Repurposing Remdesivir for COVID-19: Computational Drug Design Targeting SARS-CoV-2 RNA Polymerase and Main Protease using Molecular Dynamics Approach
• Inclusion of glycopeptides in hydrogen/deuterium exchange mass spectrometry analysis of SARS-CoV-2 spike ectodomain provides increased sequence coverage -
  Hydrogen/deuterium exchange mass spectrometry (HDX-MS) can provide precise analysis of a protein's conformational dynamics across varied states, such as heat-denatured vs. native protein structures, localizing regions that are specifically affected by such conditional changes. Maximizing protein sequence coverage provides high confidence that regions of interest were located by HDX-MS, but one challenge for complete sequence coverage is N-glycosylation sites. The deuteration of glycopeptides has not always been identified in previous reports of HDX-MS analyses, causing significant sequence coverage gaps in heavily glycosylated proteins and uncertainty in structural dynamics in many regions throughout a glycoprotein. We report HDX-MS analysis of the SARS-CoV-2 spike protein ectodomain in its trimeric pre-fusion form, which has 22 predicted N-glycosylation sites per monomer, with and without heat treatment. We identified glycopeptides and calculated their isotopic mass shifts from deuteration. Inclusion of the deuterated glycopeptides increased sequence coverage of spike ectodomain from 76% to 84%, demonstrated that glycopeptides had been deuterated, and improved confidence in results localizing structural re-arrangements. Inclusion of deuterated glycopeptides improves the analysis of the conformational dynamics of glycoproteins such as viral surface antigens and cellular receptors.
  🖺 Full Text HTML: Inclusion of glycopeptides in hydrogen/deuterium exchange mass spectrometry analysis of SARS-CoV-2 spike ectodomain provides increased sequence coverage

From Clinical Trials

• Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions:   COVID-19;   COVID-19 Pandemic
  Interventions:   Behavioral: COVID-19 walk-up, on-site testing strategy;   Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders;   Behavioral: No-cost self-testing kit vending machines
  Sponsors:   University of California, San Diego;   San Ysidro Health Center
  Not yet recruiting

• Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Other: manual therapy;   Other: breathing exercise and prone position alone
  Sponsor:   Cairo University
  Completed

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition:   Covid19
  Interventions:   Other: Placebo;   Drug: Montelukast
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition:   Covid19
  Interventions:   Drug: Fluvoxamine;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600) - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100) - Condition:   Covid19
  Interventions:   Drug: Fluvoxamine;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• Safety Study of COVID19 Vaccine on the Market - Condition:   COVID-19
  Intervention:   Biological: Recombinant new coronavirus vaccine (CHO cell)
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention;   Guizhou Center for Disease Control and Prevention;   Hainan Center for Disease Control & Prevention
  Recruiting

• Pycnogenol® in Post-COVID-19 Condition - Conditions:   Post COVID-19 Condition;   Long COVID
  Interventions:   Drug: Pycnogenol®;   Drug: Placebo
  Sponsor:   University of Zurich
  Recruiting

• Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions:   Pulmonary Fibrosis;   COVID-19 Pneumonia
  Intervention:   Drug: Bailing capsule
  Sponsor:   Second Affiliated Hospital, School of Medicine, Zhejiang University
  Not yet recruiting

• A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation - Conditions:   COVID-19;   Hematopoietic Stem Cell Transplantation
  Intervention:   Biological: COVID Convalescent Plasma
  Sponsor:   Institute of Hematology & Blood Diseases Hospital
  Recruiting

• Evaluating Emetine for Viral Outbreaks (EVOLVE) - Condition:   COVID-19
  Interventions:   Drug: Emetine Hydrochloride;   Drug: Placebo
  Sponsors:   Johns Hopkins University;   Nepal Health Research Council;   Bharatpur Hospital Chitwan;   Stony Brook University;   Rutgers University
  Not yet recruiting

• Cupping Therapy on Immune System in Post Covid -19 - Condition:   Covid-19 Patients
  Interventions:   Combination Product: Cupping therapy with convential medical treatment;   Drug: Convential medical treatment
  Sponsor:   Cairo University
  Completed

• To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition:   COVID-19
  Intervention:   Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)
  Sponsor:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
  Completed

• LIAISON NES Flu A/B & COVID-19 Clinical Agreement - Conditions:   Influenza A;   Influenza Type B;   Coronavirus Disease 2019
  Intervention:   Diagnostic Test: LIAISON NES FLU A/B & COVID-19
  Sponsor:   DiaSorin Molecular LLC
  Not yet recruiting

• Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV) - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 DNA Vaccine (ICCOV)
  Sponsors:   Immuno Cure 3 Limited;   The University of Hong Kong
  Recruiting

From PubMed

• Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation - CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.

• Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2 - COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent…

• Tocilizumab for the treatment of COVID-19 - INTRODUCTION: Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders.

• Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review - The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people’s general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties of…

• COVID-19 PCR: frequency of internal control inhibition in clinical practice - CONCLUSIONS: This study showed a low percentage of inhibition using RNase P as an internal control in COVID-19 PCRs using the CDC protocol, thus proving the effectiveness of this protocol for identification of SARS-CoV-2 in clinical samples. Re-extraction was efficacious for samples that showed little or no fluorescence for the RNase P gene.

• A suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study - In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for…

• Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV - The main protease (M^(pro)) of SARS-CoV-2 is essential for viral replication, which suggests that the M^(pro) is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 M^(pro) in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 M^(pro) in cis- and trans-cleavage proteolytic assays….

• Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing…

• An allosteric inhibitor of sirtuin 2 deacetylase activity exhibits broad-spectrum antiviral activity - Most drugs used to treat viral disease target a virus-coded product. They inhibit a single virus or virus family, and the pathogen can readily evolve resistance. Host-targeted antivirals can overcome these limitations. The broad-spectrum activity achieved by host targeting can be especially useful in combating emerging viruses and for treatment of diseases caused by multiple viral pathogens, such as opportunistic agents in immunosuppressed patients. We have developed a family of compounds that…

• Recent advances in RNA sample preparation techniques for the detection of SARS-CoV-2 in saliva and gargle - Molecular detection of SARS-CoV-2 in gargle and saliva complements the standard analysis of nasopharyngeal swabs (NPS) specimens. Although gargle and saliva specimens can be readily obtained non-invasively, appropriate collection and processing of gargle and saliva specimens are critical to the accuracy and sensitivity of the overall analytical method. This review highlights challenges and recent advances in the treatment of gargle and saliva samples for subsequent analysis using reverse…

• An efflux pump in genomic island GI-M202a mediates the transfer of polymyxin B resistance in Pandoraea pnomenusa M202 - CONCLUSIONS: These findings demonstrated that GI-M202a along with the MFS transporter FKQ53_RS21695 in P. pnomenusa M202 could mediate the transmission of polymyxin B resistance.

• Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon - Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and…

• Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor - Acute lung injury is significantly associated with the aberrant activation and pyroptosis of alveolar macrophages. Targeting the GPR18 receptor presents a potential therapeutic approach to mitigate inflammation. Verbenalin, a prominent component of Verbena in Xuanfeibaidu (XFBD) granules, is recommended for treating COVID-19. In this study, we demonstrate the therapeutic effect of verbenalin on lung injury through direct binding to the GPR18 receptor. Verbenalin inhibits the activation of…

• Synthesis, Characterization, and Antibacterial Activity of New Isatin Derivatives - 1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by…

• Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication - The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro’s restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that…

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