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<title>31 October, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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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>Forecasting Influenza-Like Illness (ILI) during the COVID-19 Pandemic</strong> -
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Near-term probabilistic forecasts for infectious diseases such as COVID-19 and influenza play an important role in public health communication and policymaking. From 2013-2019, the FluSight challenge run by the Centers for Disease Control and Prevention invited researchers to develop and submit forecasts using influenza-like illness (ILI) as a measure of influenza burden. Here we examine how several statistical models and an autoregressive neural network model perform for forecasting ILI during the COVID-19 pandemic, where historical patterns of ILI were highly disrupted. We find that the autoregressive neural network model which forecasted ILI well pre-COVID still performs well for some locations and forecast horizons, but its performance is highly variable, and performs poorly in many cases. We found that a simple exponential smoothing statistical model is in the top half of ranked models we evaluated nearly 75% of the time. Our results suggest that even simple statistical models may perform as well as or better than more complex machine learning models for forecasting ILI during the COVID-19 pandemic. We also created an ensemble model from the limited set of time series forecast models we created here. The limited ensemble model was rarely the best or the worst performing model compared to the rest of the models assessed, confirming previous observations from other infectious disease forecasting efforts on the less variable and generally favorable performance of ensemble forecasts. Our results support previous findings that no single modeling approach outperforms all other models across all locations, time points, and forecast horizons, and that ensemble forecasting consortia such as the COVID-19 Forecast Hub and FluSight continue to serve valuable roles in collecting, aggregating, and ensembling forecasts using fundamentally disparate modeling strategies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281617v1" target="_blank">Forecasting Influenza-Like Illness (ILI) during the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: A retrospective cohort study</strong> -
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Objective: To investigate temporal trends, severe outcomes, and rebound among systemic autoimmune rheumatic disease (SARD) patients according to outpatient SARS-CoV-2 treatment. Methods: We performed a retrospective cohort study investigating outpatient SARS-CoV-2 treatments among SARD patients at Mass General Brigham (23/Jan/2022-30/May/2022). We identified SARS-CoV-2 infection by positive PCR or antigen test (index date=first positive test) and SARDs using diagnosis codes and immunomodulator prescription. Outpatient treatments were confirmed by medical record review. The primary outcome was hospitalization or death within 30 days following the index date. COVID-19 rebound was defined as documentation of negative then newly-positive SARS-CoV-2 tests. The association of any vs. no outpatient treatment with hospitalization/death was assessed using multivariable logistic regression. Results: We analyzed 704 SARD patients with COVID-19 (mean age 58.4 years, 76% female, 49% with rheumatoid arthritis). Treatment as outpatient increased over calendar time (p<0.001). A total of 426(61%) received outpatient treatment: 307(44%) with nirmatrelvir/ritonavir, 105(15%) with monoclonal antibodies, 5(0.7%) with molnupiravir, 3(0.4%) with outpatient remdesivir, and 6(0.9%) with combinations. There were 9/426 (2.1%) hospitalizations/deaths among those treated as outpatient compared to 49/278 (17.6%) among those with no outpatient treatment (adjusted odds ratio [aOR] 0.12, 0.05 to 0.25). 25/318 (8%) of patients who received oral outpatient treatment had documented COVID-19 rebound. Conclusion: Outpatient treatment was strongly associated with lower odds of severe COVID-19 compared to no outpatient treatment. At least 8% of SARD patients experienced COVID-19 rebound. These findings highlight the importance of outpatient COVID-19 treatment for SARD patients and the need for further research on rebound.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281629v1" target="_blank">Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: A retrospective cohort study</a>
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</div></li>
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<li><strong>Application of a Multiplicative Cascade Model to Detect the Early Signs of SARS-CoV-2 Infection Using Heart Rate Data</strong> -
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Background: Wrist-worn devices can keep track of a persons daily health status, including those likely to become infected with the SARS-CoV-2 virus. Technological solutions using mobile devices are being developed to predict the time course of COVID-19. Objective: In this proof-of-concept study, we use heart rate data to detect the first sign of infection in people who have been diagnosed with COVID-19 and to monitor the time-course of the illness. Methods: The heart-rate data were analysed using a multiplicative cascade driven by a Gaussian process. This provides two parameters, mean and standard deviation, which when combined with similar parameters estimated from control series, provide a Health Index. Results: For 90% of 31 cases, the Health Index tracked COVID-19 infection with the virus and subsequent recovery. The first sign of COVID-19 was detected on average nine days before symptoms were reported. Conclusions: Early detection of COVID-19 may lead to a reduction in the spread of the virus. The Heath Indexs potential use for the early detection of complications arising from Long COVID would be an important innovation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281632v1" target="_blank">Application of a Multiplicative Cascade Model to Detect the Early Signs of SARS-CoV-2 Infection Using Heart Rate Data</a>
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</div></li>
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<li><strong>Protection against reinfection with SARS-CoV-2 omicron BA.2.75* sublineage</strong> -
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The BA.2.75* sublineage of SARS-CoV-2 B.1.1.529 (omicron) variant escapes neutralizing antibodies. We estimated effectiveness of prior infection in preventing reinfection with BA.2.75* using a test-negative, case-control study design. Effectiveness of prior pre-omicron infection against BA.2.75* reinfection, irrespective of symptoms, was 6.0% (95% CI: 1.5-10.4%). Effectiveness of prior BA.1/BA.2 infection was 49.9% (95% CI: 47.6-52.1%) and of prior BA.4/BA.5 infection was 80.6% (95% CI: 71.2-87.0). Effectiveness of prior pre-omicron infection followed by BA.1/BA.2 infection against BA.2.75* reinfection was 56.4% (95% CI: 50.5-61.6). Effectiveness of prior pre-omicron infection followed by BA.4/BA.5 infection was 91.6% (95% CI: 65.1-98.0). Analyses stratified by time since prior infection indicated waning of protection since prior infection. Analyses stratified by vaccination status indicated that protection from prior infection is higher among those vaccinated, particularly among those who combined index-virus-type vaccination with a prior omicron infection. A combination of pre-omicron and omicron immunity is most protective against BA.2.75* reinfection. Viral immune evasion may have accelerated recently to overcome high immunity in the global population, thereby also accelerating waning of natural immunity.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.29.22281606v1" target="_blank">Protection against reinfection with SARS-CoV-2 omicron BA.2.75* sublineage</a>
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</div></li>
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<li><strong>The relative contribution of COVID-19 infection versus COVID-19 related occupational stressors to insomnia in healthcare workers</strong> -
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Abstract Objective/Background: Healthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers. Patients/Methods: An online self-report survey was collected between September 2020 and July 2022 from N=594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors. Results: Insomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (Beta=1.7+/-0.14SE, Beta=0.08+/-0.03, and Beta=0.69+/-0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items. Conclusions: Both recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rate of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281582v1" target="_blank">The relative contribution of COVID-19 infection versus COVID-19 related occupational stressors to insomnia in healthcare workers</a>
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<li><strong>Results of safety monitoring of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in U.S. children aged 5-17 years</strong> -
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Importance: Active monitoring of health outcomes following COVID-19 vaccination offers early detection of rare outcomes that may not be identified in pre-licensure trials. Objective: To conduct near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years. Design: We conducted rapid cycle analysis of 20 pre-specified health outcomes, 13 of which underwent sequential testing and 7 of which were monitored descriptively within a cohort of vaccinated individuals. We tested for increased risk of each health outcome following vaccination compared to a historical baseline, while adjusting for repeated looks at the data as well as claims processing delay. Setting: This is a population-based study in three large commercial claims databases conducted under the U.S. FDA public health surveillance mandate. Participants: The study included over 3 million enrollees aged 5-17 years with BNT162b2 COVID-19 vaccination through mid-2022 in three commercial claims databases. We required continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (Dose 1 + Dose 2), and dose-specific secondary analyses were conducted. Follow up time was censored for death, disenrollment, end of risk window, end of study period, or a subsequent vaccine dose. Main Outcome(s) and Measure(s): We monitored 20 pre-specified health outcomes. We performed descriptive monitoring for all outcomes and sequential testing for 13 outcomes. Results: Among 13 health outcomes evaluated by sequential testing, 12 did not meet the threshold for a statistical signal in any of the three databases. In our primary analysis, myocarditis/pericarditis signaled following primary series vaccination with BNT162b2 in ages 12-17 years across all three databases. Conclusions and Relevance: Consistent with published literature, our near-real time monitoring identified a signal for only myocarditis/pericarditis following BNT162b2 COVID-19 vaccination in children aged 12-17 years. This method is intended for early detection of safety signals. Our results are reassuring of the safety of the vaccine, and the potential benefits of vaccination outweigh the risks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281532v1" target="_blank">Results of safety monitoring of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in U.S. children aged 5-17 years</a>
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<li><strong>Scenario modelling for diminished influenza seasons during 2020/2021 and 2021/2022 in England</strong> -
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<b>Background:</b> There has been concern throughout the COVID-19 pandemic over highly stressed healthcare capacities being further pressured by seasonal influenza epidemics. Interventions to tackle the spread of SARS-CoV-2, the causative agent of COVID-19, have unsettled the respiratory pathogen landscape, including worldwide patterns of influenza activity. The implications of these disruptions for subsequent influenza seasons has been uncertain. <b>Methods:</b> To conduct scenario analyses ahead of the 2020/2021 and 2021/2022 influenza seasons in England, we used a pre-existing age-structured, multi-strain compartmental model of influenza transmission and case severity, which included propagation of immunity between influenza seasons and had been previously fit to historical data. For the pre-2020/2021 influenza season, our scenarios varied the level of vaccine uptake and the inclusion/exclusion of nonpharmaceutical interventions (NPIs). We estimated the relative amount of health episode occurrences: symptomatic cases resulting in a GP consultation, hospital inpatient admissions, fatalities. In the pre-2021/2022 influenza season analysis, compared with a counterfactual case where influenza activity remained at historic levels in the 2020/2021 influenza season, we estimated the change in the same set of health episode occurrences in the 2021/2022 influenza season when assuming there was no influenza in circulation during the 2020/2021 influenza season. <b>Results:</b> Attaining coverage of 75% in target groups for the 2020/2021 influenza season reduced health episode occurrences by 40-50% when compared to maintaining the 2019/2020 vaccination programme coverage and uptake levels. Having NPIs maintained throughout the entire influenza season saw 60-80% reductions in severe case outcomes. Combining an expanded vaccination programme and the use of NPIs could suppress the seasonal influenza epidemic, with reductions as much as 90-100%. In the absence of influenza transmission during the 2020/2021 influenza season, under our modelling assumption of mixing patterns returning to pre-2020 levels we projected a compensatory influenza epidemic with 1.2 to 2.2 times as many severe health episode occurrences in the subsequent 2021/2022 influenza season. <b>Conclusions:</b> In the context of the time the work was originally conducted, the modelled scenarios indicated how bolstering vaccine coverage and reduction in contacts could likely allay resurgent seasonal influenza epidemics. Our analyses of the winter pressures that may be inflicted by other respiratory infections during the COVID-19 pandemic are one example of the modelling insights provided to the Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) for the Scientific Advisory Group for Emergencies (SAGE) in the UK.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281628v1" target="_blank">Scenario modelling for diminished influenza seasons during 2020/2021 and 2021/2022 in England</a>
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<li><strong>Identifying trends in SARS-CoV-2 RNA in wastewater to infer changing COVID-19 incidence: Effect of sampling frequency</strong> -
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SARS-CoV-2 RNA concentrations in wastewater solids and liquids are correlated with reported incident COVID-19 cases. Reporting of incident COVID-19 cases has changed dramatically with the availability of at-home antigen tests. Wastewater monitoring therefore represents an objective tool for continued monitoring of COVID-19 occurrence. One important use case for wastewater data is identifying when there are sustained changes or trends in SARS-CoV-2 RNA concentrations. Such information can be used to inform public health messaging, testing, and vaccine resources. However, there is limited research on best approaches for identifying trends in wastewater monitoring data. To fill this knowledge gap, we applied three trend analysis methods (relative strength index (RSI), percent change (PC), Mann-Kendall (MK) trend test) to daily measurements of SARS-CoV-2 RNA in wastewater solids from a wastewater treatment plant to characterize trends. Because daily measurements are not common for wastewater monitoring programs, we also conducted a downsampling analysis to determine the minimum sampling frequency necessary to capture the trends identified using the gold standard daily data. The PC and MK trend test appear to perform similarly and better than the RSI in terms of early warning signaling for increasing and decreasing trends, so we only considered the PC and MK trend test methods in the downsampling analysis. Using an acceptable sensitivity and specificity cutoff of 0.5, we found that a minimum of 4 samples/week and 5 samples/week is necessary to detect trends identified by daily sampling using the PC and MK trend test method, respectively. If a higher sensitivity and specificity is needed, then more samples per week would be needed. Public health officials can adopt these trend analysis approaches and sampling frequency recommendations to wastewater monitoring programs aimed at providing information on how incident COVID-19 cases are changing in the contributing communities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281667v1" target="_blank">Identifying trends in SARS-CoV-2 RNA in wastewater to infer changing COVID-19 incidence: Effect of sampling frequency</a>
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<li><strong>Potential risk polarization for acute myocardial infarction during the COVID-19 pandemic: Single-center experiences in Osaka, Japan</strong> -
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This study compared the time course and outcomes of acute myocardial infarction, including mechanical complications and hospital mortality, before and after the coronavirus disease 2019 (COVID-19) pandemic at a regional core hospital in South Osaka, Japan. Moreover, it identified predictors for hospital mortality and mechanical complications. In total, 503 patients who underwent emergency percutaneous coronary intervention between January 2011 and December 2021 at our institution were examined retrospectively. The time course of acute myocardial infarction, mechanical complications, and mortality rate before and after the COVID-19 emergency declaration were compared. Overall, 426 patients with ST-segment elevation myocardial infarction and 77 patients with non-ST-segment elevation myocardial infarction were identified. For patients with ST-segment elevation myocardial infarction, the onset-to-door time was longer (181 vs. 156 min, P = 0.001) and mechanical complications were worse (7.8% vs. 2.6%, P = 0.025) after the emergency declaration of COVID-19 than before the pandemic. Age, low ejection fraction, out-of-hospital cardiac arrest, and mechanical complications were identified as independent risk factors for hospital mortality among patients with ST-segment elevation myocardial infarction, using multivariable analysis. Post-declaration, age, walk-ins, referrals, and intra-aortic balloon pump use were independent predictors of mechanical complications among patients with ST-segment elevation myocardial infarction. Onset-to-door time and mechanical complication rate increased after the COVID-19 declaration among patients with ST-segment elevation myocardial infarction. Arrival by walk-in and a referral that caused treatment delay were identified as independent risk factors for mechanical complication, in addition to age, use of intra-aortic balloon pump, and post-declaration of COVID-19. Therefore, the risks posed by the COVID-19 pandemic might have a polarization tendency resulting from the relief or worsening of cardiac symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281657v1" target="_blank">Potential risk polarization for acute myocardial infarction during the COVID-19 pandemic: Single-center experiences in Osaka, Japan</a>
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<li><strong>Reporting of medication adherence in randomized controlled trials of pharmacological interventions for SARS-CoV-2: a cross-sectional analysis</strong> -
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Background: Adherence to pharmacological interventions in clinical trials is crucial for correct estimation of beneficial and adverse effects, including trials of SARS-CoV-2. The Template for Intervention Description and Replication (TIDieR), a 12-item extension of the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines, includes two items (11 and 12) that address intervention adherence reporting in trial publications. Objective: To assess compliance with TIDieR items 11 and 12 of randomised controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in five selected journals during 2021. Methods: We assessed SARS-CoV-2 pharmacological RCTs published in the Annals of Internal Medicine, The BMJ, JAMA, The Lancet, and The New England Journal of Medicine in 2021 for compliance with TIDieR items 11 and 12. Item 11 was assessed in two parts: 11a how intervention adherence was assessed; 11b if any strategies were used to maintain or improve how intervention adherence was maintained or improved. Item 12 assessed the extent to which the intervention was delivered as planned. We calculated raw adherence and proportional (weighted) adherence for pharmacological and comparator interventions where available. Results: We found 75 eligible RCTs, of which 28 (37%) reported results related to SARS-CoV-2 vaccinations. Compliance with items 11a and 12 could be assessed in 71 of these 75. Of those 71 RCTs, 37 (52%, 95% confidence interval 40 to 64%) were compliant with reporting of item 11a. Seven RCTs had a strategy to assess compliance with item 11b, and only three (43%, 9 to 82%) of those complied with item 11b reporting. Of the 71 RCTs, 70 complied with reporting of item 12. Only one of the 71 RCTs (1.4%, 0 to 7.6%) fully complied with TIDieR items 11a, 11b, and 12. Compliance varied across journals. Conclusions: RCTs of SARS-CoV-2 pharmacological interventions published in high-impact medical journals complied variably with reporting of intervention adherence, even though the journals endorse CONSORT. The implications for interpretation, application, and replication of findings based on these publications warrant consideration.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.30.22281709v1" target="_blank">Reporting of medication adherence in randomized controlled trials of pharmacological interventions for SARS-CoV-2: a cross-sectional analysis</a>
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<li><strong>Preliminary report: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, KD-414, in healthy adult participants: a non-randomized, open-label phase 2/3 clinical study in Japan</strong> -
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Abstract: Background: In the prolonged COVID-19 pandemic, there remains a high need for the development of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine that can be used more safely and effectively to prevents the disease onset or severe disease. To satisfy such unmet need, we are currently developing the inactivated whole particle SARS-CoV-2 vaccine (KD-414) and conducted a phase 2/3 study in healthy adults in Japan to accumulate more immunogenicity and safety data of KD-414 using the dose selected based on the results of the phase 1/2 study. Methods: In an open-label uncontrolled phase 2/3 study, adults aged 18 years or older without a history of COVID-19 or COVID-19 vaccination received two intramuscular doses of KD-414 at a 28-day intervals, followed by one intramuscular dose 13 weeks after the second dose as the primary immunization. Safety data were collected after the first dose of KD-414 in all participants to evaluate the safety profile. In predetermined immunogenicity analysis subjects, the neutralizing antibody titers against the pseudovirus SARS-CoV-2 (Wuhan) before the first vaccination and after each vaccination with KD-414 were evaluated. Results: A total of 2500 adults aged 18 years or older were enrolled; 2474 of them received the vaccination up to the second dose, and 2081 completed the third vaccination. Regarding the safety, no deaths or serious adverse reactions were recorded from the first vaccination until 28 days after the third vaccination with KD-414. The incidence of adverse reactions (number of participants with onsets/number of participants in the safety analysis set) was 80.6% (2015/2500). Adverse reactions with an incidence of 10% or more included injection site pain, malaise, headache, injection site erythema, myalgia, and injection site induration. A total of 11 events of grade 3 or higher adverse reactions that prevented daily activities in 9 participants. There was no increasing tendency in the incidence of adverse reactions responding to the vaccinations. To evaluate immunogenicity, 295 first comers enrolled from five age ranges were allocated to the immunogenicity analysis subjects; 291 participants received the vaccination up to the second dose, and 249 participants completed the third vaccination. The geometric mean titers (95% confidence interval [CI]) of neutralizing antibody titers against pseudovirus SARS-CoV-2 (Wuhan) 28 days after the second vaccination and 28 days after the third vaccination with KD-414 were 139.6 (118.9 - 164.0) and 285.6 (244.3 - 334.0), respectively, showing an approximately two-fold increase after the third vaccination compared to that after the second vaccination. The geometric mean titers (95% CI) of neutralizing antibody titers after the third vaccination were 327.6 (269.8 - 397.9), 272.2 (211.5 - 350.4) and 128.0 (51.6 - 317.7) in participants aged 18 to 40 years, 41 to 64 years, and 65 years or older, respectively, showing an age-dependency. Conclusion: This study confirmed the favorable safety profile of KD-414 as a result of three vaccinations of KD-414 administered to over 2000 healthy Japanese participants aged 18 years or older. There were no particular differences in the types and incidences of adverse reactions between vaccinations, and no tendency of an increase in adverse reactions with an increase in the number of vaccinations. Similar to the phase 1/2 study, neutralizing antibody responses appeared to be age-dependent and the highest titers were observed in the age group of 18 - 40 years. A phase 3 study in adults aged 18 - 40 years (jRCT2031210679) and a phase 2/3 study in children aged 6 months - 18 years (jRCT2031220032) are currently ongoing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.27.22281603v1" target="_blank">Preliminary report: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, KD-414, in healthy adult participants: a non-randomized, open-label phase 2/3 clinical study in Japan</a>
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<li><strong>Seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and adolescents in Montreal, Canada</strong> -
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Importance: Repeated serological testing for SARS-CoV-2 allows the monitoring of antibody dynamics in populations, including detecting infections that are missed by RT-PCR or antigen testing. Understanding the factors associated with seroconversion and seroreversion as well as the duration of infection-induced antibodies can also inform public health recommendations regarding disease prevention and mitigation efforts. Objective: To use serological testing to assess the prevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. Design: This analysis reports on three rounds of data collection from a prospective cohort study (Enfants et COVID-19: Étude de séroprévalence [EnCORE]). The study rounds occurred as follows: Round 1 October 2020-March 2021, Round 2 May to July 2021, and Round 3 November 2021 to January 2022. Most Round 3 samples were collected prior to the spread of the Omicron BA.1 variant in Quebec. Setting: Population-based sample. Participants: Children and adolescents aged 2 to 17 years in Montreal, Canada. Exposure: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: Participants provided dried blood spots (DBS) for antibody detection and parents completed online questionnaires for sociodemographics and COVID-19 symptoms and testing history. The serostatus of participants was determined by enzyme-linked immunosorbent assays (ELISAs) using the receptor-binding domain (RBD) from the spike protein and the nucleocapsid protein (N) as antigens. We estimated seroprevalence for each round of data collection and by participant and household characteristics. Seroconversion rates were calculated as were the likelihoods of remaining seropositive at six months and one year. Results: The study included DBS samples from 1 632, 936, and 723 participants in the first, second, and third rounds of data collection, respectively. The baseline seroprevalence was 5.8% (95% CI 4.8-7.1), which increased to 10.5% and 10.9% for the respective follow-ups (95% CI 8.6-12.7; 95% CI 8.8-13.5). The overall average crude rate of seroconversion over the study period was 12.7 per 100 person-years (95% CI 10.9-14.5). Adjusted hazard rates of seroconversion by child and household characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. The likelihood of remaining seropositive at six months was 67% (95% CI 59-76) and dropped to 19% (95% CI 11%-33%) at one year. Conclusions and Relevance: The data reported here provide estimates of pre-Omicron seroprevalence, seroconversion rates and time to seroreversion in a population-based cohort of children and adolescents. Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels following infection. Continued study of seroconversion and seroreversion can inform public health recommendations such as COVID-19 vaccination and booster schedules.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281660v1" target="_blank">Seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and adolescents in Montreal, Canada</a>
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<li><strong>Machine learning models for predicting severe COVID-19 outcomes in hospitals</strong> -
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Objectives The aim of this observational retrospective study is to improve early risk stratification of hospitalized Covid-19 patients by predicting in-hospital mortality, transfer to intensive care unit (ICU) and mechanical ventilation from electronic health record data of the first 24 hours after admission. Methods and Results Our machine learning model predicts in-hospital mortality (AUC=0.918), transfer to ICU (AUC=0.821) and the need for mechanical ventilation (AUC=0.654) from a few laboratory data of the first 24 hours after admission. Models based on dichotomous features indicating whether a laboratory values exceeds or falls below a threshold perform nearly as good as models based on numerical features. Conclusions We devise completely data-driven and interpretable machine-learning models for the prediction of in-hospital mortality, transfer to ICU and mechanical ventilation for hospitalized Covid-19 patients within 24 hours after admission. Numerical values of CRP and blood sugar and dichotomous indicators for increased partial thromboplastin time (PTT) and glutamic oxaloacetic transaminase (GOT) are amongst the best predictors.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281646v1" target="_blank">Machine learning models for predicting severe COVID-19 outcomes in hospitals</a>
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<li><strong>Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A</strong> -
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Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s). VHH fusion with the canonical immunoglobulin Fc fragment allows the Fc-fusion single-domain antibodies (VHH-Fc) to significantly increase their neutralizing activity and serum half-life. Previously we have developed and characterized VHH-Fc specific to botulinum neurotoxin A (BoNT/A), that showed a 1000-fold higher protective activity than monomeric form when challenged with five times the lethal dose (5 LD50) of BoNT/A. During the COVID-19 pandemic, mRNA vaccines based on lipid nanoparticles (LNP) as a delivery system have become an important translational technology that has significantly accelerated the clinical introduction of mRNA platforms. We have developed an mRNA platform that provides long-term expression after both intramuscular and intravenous application. The platform has been extensively characterized using firefly luciferase (Fluc) as a reporter. An intramuscular administration of LNP-mRNA encoding VHH-Fc antibody made it possible to achieve its rapid expression in mice and resulted in 100% protection when challenged with up to 100 LD50 of BoNT/A. The presented approach for the delivery of sdAbs using mRNA technology greatly simplifies drug development for antibody therapy and can be used for emergency prophylaxis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.29.514343v1" target="_blank">Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A</a>
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<li><strong>Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study</strong> -
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Background Analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data from household infections should aid its detailed epidemiological understanding. Using viral genomic sequence data, we investigated household SARS-CoV-2 transmission and evolution in coastal Kenya households. Methods We conducted a case-ascertained cohort study between December 2020 and February 2022 whereby 573 members of 158 households were prospectively monitored for SARS-CoV-2 infection. Households were invited to participate if a member tested SARS-CoV-2 positive or was a contact of a confirmed case. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Positive samples with an RT-PCR cycle threshold of <33.0 were subjected to whole genome sequencing followed by phylogenetic analysis. Ancestral state reconstruction was used to determine if multiple viruses had entered households. Results Of 2,091 NP/OP swabs that were collected, 375 (17.9%) tested SARS-CoV-2 positive. Viral genome sequences (>80% coverage) were obtained from 208 (55%) positive samples obtained from 61 study households. These genomes fell within 11 Pango lineages and four variants of concern (Alpha, Beta, Delta and Omicron). We estimated 163 putative transmission events involving members of the sequenced households, 40 (25%) of which were intra-household transmission events while 123 (75%) were infections that likely occurred outside the households. Multiple virus introductions (up-to-5) were observed in 28 (47%) households with the 1-month follow-up period. Conclusions We show that a considerable proportion of SARS-CoV-2 infections in coastal Kenya occurred outside the household setting. Multiple virus introductions frequently occurred into households within the same infection wave in contrast to observations from high income settings, where single introduction appears to be the norm. Our findings suggests that control of SARS-CoV-2 transmission by household member isolation may be impractical in this setting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.26.22281455v1" target="_blank">Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study</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>Safety and Efficacy of Medications COVID-19</strong> - <b>Condition</b>: Severe Covid-19<br/><b>Intervention</b>: Drug: Oral bedtime melatonin<br/><b>Sponsor</b>: Hospital San Carlos, Madrid<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma<br/><b>Sponsors</b>: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Molnupiravir (Esperavir); Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Tri-City COVID Attitudes Study<br/><b>Sponsor</b>: University of Kansas Medical Center<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>Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms</strong> - <b>Conditions</b>: Covid19; Post-acute COVID-19 Syndrome<br/><b>Interventions</b>: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program<br/><b>Sponsors</b>: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>JT001 (VV116) for the Treatment of COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH<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>Boost Intentions and Facilitate Action to Promote COVID-19 Booster Take-up</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine<br/><b>Sponsor</b>: University of California, Los Angeles<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>Effects of Prompt to Bundle COVID-19 Booster and Flu Shot</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle<br/><b>Sponsor</b>: University of California, Los Angeles<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>Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms<br/><b>Sponsor</b>: University of California, Los Angeles<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>Respiratory Muscles After Inspiratory Muscle Training After COVID-19</strong> - <b>Conditions</b>: COVID-19; Diaphragm Injury<br/><b>Intervention</b>: Device: Inspiratory Muscle Training (IMT)<br/><b>Sponsors</b>: RWTH Aachen University; Philipps University Marburg Medical Center<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>OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial</strong> - <b>Conditions</b>: COVID-19; Immunodeficiency<br/><b>Interventions</b>: Drug: Paxlovid 5 days; Drug: Paxlovid 10 days; Drug: Tixagevimab and Cilgavimab<br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; University Hospital, Geneva<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza</strong> - <b>Conditions</b>: Influenza, Human; COVID-19<br/><b>Interventions</b>: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV<br/><b>Sponsors</b>: BioNTech SE; 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>Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Drug: ASC10; Drug: Placebo<br/><b>Sponsor</b>: Ascletis Pharmaceuticals Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<br/><b>Completed</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>Inosine: a broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation</strong> - SARS-CoV-2-induced cytokine storms constitute the primary cause of COVID-19 progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies have been frequently administered to treat COVID-19 but have had limited clinical efficacy in severe and critical cases. Nevertheless, the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection. We found that the broad-spectrum anti-inflammatory agent inosine…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In vitro</em> effect of <em>Withania somnifera</em>, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb-drug interactions in the management of COVID-19</strong> - Ayurvedic medicines Withania somnifera Dunal (ashwagandha) and AYUSH-64 have been used for the prevention and management of COVID-19 in India. The present study explores the effect of Ashwagandha and AYUSH-64 on important human CYP enzymes (CYP3A4, CYP2C8, and CYP2D6) to assess their interaction with remdesivir, a drug used for COVID-19 management during the second wave. The study also implies possible herb-drug interactions as ashwagandha and AYUSH-64 are being used for managing various…</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>Use of natural cysteine protease inhibitors in limiting SARS-Co-2 fusion into human respiratory cells</strong> - Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of 1,4-naphthoquinone derivatives as antibacterial agents: activity and mechanistic studies</strong> - The diverse and large-scale application of disinfectants posed potential health risks and caused ecological damage during the 2019-nCoV pandemic, thereby increasing the demands for the development of disinfectants based on natural products, with low health risks and low aquatic toxicity. In the present study, a few natural naphthoquinones and their derivatives bearing the 1,4-naphthoquinone skeleton were synthesized, and their antibacterial activity against selected bacterial strains was…</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 stimulated platelets in COVID-19 thrombosis: Role of alpha7 nicotinic acetylcholine receptor</strong> - Since early 2020, SARS-CoV-2-induced infection resulted in global pandemics with high morbidity, especially in the adult population. COVID-19 is a highly prothrombotic condition associated with subsequent multiorgan failure and lethal outcomes. The exact mechanism of the prothrombotic state is not well understood and might be multifactorial. Nevertheless, platelets are attributed to play a crucial role in COVID-19-associated thrombosis. To date, platelets’ role was defined primarily in…</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>Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis</strong> - CONCLUSION: Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.</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>Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b</strong> - SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Common NLRP3 inflammasome inhibitors and Covid-19: Divide and conquer</strong> - Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A protective erythropoietin evolutionary landscape, NLRP3 inflammasome regulation, and multisystem inflammatory syndrome in children</strong> - The low incidence of pediatric severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the associated multisystem inflammatory syndrome (MIS-C) lack a unifying pathophysiological explanation, impeding effective prevention and therapy. Activation of the NACHT, LRR, and PYD domains-containing protein (NLRP) 3 inflammasome in SARS-CoV-2 with perturbed regulation in MIS-C, has been reported. We posit that, early age physiological states and genetic determinants, such as certain…</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>Uncovering novel disinfection mechanisms of solar light/periodate system: The dominance of singlet oxygen and metabolomic insights</strong> - Disinfection plays an essential role in waterborne pathogen control and disease prevention, especially during the COVID-19 pandemic. Catalyst-free solar light/periodate (PI) system has recently presented great potential in water disinfection, whereas the in-depth chemical and microbiological mechanisms for efficient bacterial inactivation remain unclear. Our work delineated firstly the critical role of singlet oxygen, instead of reported hydroxyl radicals and superoxide radicals, in dominating…</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>Employing functionalized graphene quantum dots to combat coronavirus and enterovirus</strong> - The ongoing COVID-19 (i.e., coronavirus) pandemic continues to adversely affect the human life, economy, and the world’s ecosystem. Although significant progress has been made in developing antiviral materials for the coronavirus, much more work is still needed. In this work, N-functionalized graphene quantum dots (GQDs) were designed and synthesized as the antiviral nanomaterial for Feline Coronavirus NTU156 (FCoV NTU156) and Enterovirus 71 (EV71)) with ultra-high inhibition (>99.9%). To…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Cysteine 270 as a Novel Site for Allosteric Modulators of SARS-CoV-2 Papain-Like Protease</strong> - The coronavirus papain-like protease (PLpro) plays an important role in the proteolytic processing of viral polyproteins and the dysregulation of the host immune response, providing a promising therapeutic target. However, the development of inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro is challenging owing to the restricted S1/S2 sites in the substrate binding pocket. Here we report the discovery of two activators of SARS-CoV-2 PLpro and the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight</strong> - SARS-CoV-2 is a positive-strand RNA virus that infects humans through the nasopharyngeal and oral route causing COVID-19. Scientists left no stone unturned to explore a targetable key player in COVID-19 pathogenesis against which therapeutic interventions can be initiated. This article has attempted to review, coordinate and accumulate the most recent observations in support of the hypothesis predicting the altered state of mitochondria concerning mitochondrial redox homeostasis, inflammatory…</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 Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery</strong> - Dengue fever is a mosquito-borne disease that claims the lives of millions of people around the world. A number of factors like disease’s non-specific symptoms, increased viral mutation, growing antiviral drug resistance due to reduced susceptibility, unavailability of an effective vaccine for dengue, weak immunity against the virus, and many more are involved. Dengue belongs to the Flaviviridae family of viruses. The two species of the vector transmitting dengue are Aedes aegypti and Aedes…</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>Antibody protection from SARS-CoV-2 respiratory tract exposure and infection</strong> - The COVID-19 pandemic has underscored the need to understand the dynamics of SARS-CoV-2 respiratory infection and protection provided by the immune response. SARS-CoV-2 infections are characterized by a particularly high viral load, and further by the small number of inhaled virions sufficient to generate a high viral titer in the nasal passage a few days after exposure. SARS-CoV-2 specific antibodies (Ab), induced from vaccines, previous infection, or inhaled monoclonal Ab, have proven…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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