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188 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>12 September, 2022</title>
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div.column{display: inline-block; vertical-align: top; width: 50%;}
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Purchasing Decisions in the New Normal Period: Implementation of Digital Marketing, Brand Awareness, and Viral Marketing at Shopee E-Commerce on the Use of SPayLater</strong> -
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Indonesia has one of the highest levels of e-commerce in the world, with around 97% of internet users looking for products and services to buy online. Visits to online retailers are made by him 92% of all Internet users. 94% of internet users alsо pay for prоducts and services оnline. With 94.7 million monthly visits, Shopee is the most popular online shopping destination for Indonesians. This study’s goal was to assess the effects of partially or simultaneously the application of digital marketing, brand awareness and Viral Marketing in e-commerce shopee оn the use оf SPayLatter оn purchasing decisiоns during the new normal period after the COVID-19 pandemic. The sample of this research used stratified random sampling method. The sample of this research is 100 shoppe consumer respondents. In this study, the data was analyzed using multiple regressiоn with the variant-based SEM methоd, which was assisted by SmartPLS software. Data collection using Google Forms survey. The study found that the use of digital marketing, brand awareness, and viral marketing has a partial and simultaneous positive effect on purchasing decisions following the COVID-19 pandemic, but has a weak effect on purchasing decisions.
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🖺 Full Text HTML: <a href="https://osf.io/7tr3a/" target="_blank">Purchasing Decisions in the New Normal Period: Implementation of Digital Marketing, Brand Awareness, and Viral Marketing at Shopee E-Commerce on the Use of SPayLater</a>
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<li><strong>Targeting intracellular Neu1 for Coronavirus Infection Treatment</strong> -
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There are no effective therapies for COVID-19 or antivirals against SARS-CoV-2. Furthermore, current vaccines appear less efficacious for new SARS-CoV-2 variants. Thus, there is an urgent need to better understand the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Here, we show host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest that Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.09.507342v1" target="_blank">Targeting intracellular Neu1 for Coronavirus Infection Treatment</a>
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<li><strong>Treatment with anti-inflammatory viral serpin modulates immuno-thrombotic responses and improves outcomes in SARS-CoV-2 infected mice</strong> -
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Severe acute respiratory distress syndrome (ARDS) during SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection, manifests as uncontrolled lung inflammation and systemic thrombosis with high mortality. Anti-viral drugs and monoclonal antibodies can reduce COVID-19 severity if administered in the early viremic phase, but treatments for later stage immuno-thrombotic syndrome and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases during thrombotic, thrombolytic and immune responses. The myxoma poxvirus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated coagulation and complement protease pathways as part of a self-defense strategy to combat viral clearance by the innate immune system. When purified and utilized as an anti-immune therapeutic, Serp-1 is effective as an anti-inflammatory drug in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 (PEGSerp-1) as a therapy for immuno-thrombotic complications during ARDS. Treatment with PEGSerp-1 in two distinct mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved clinical outcomes. PEGSerp-1 significantly reduced M1 macrophage invasion in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR) and complement membrane attack complex (MAC). Sequential changes in urokinase-type plasminogen activator receptor (uPAR) and serpin gene expression were observed in lung and heart with PEGSerp-1 treatment. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for treatment of severe viral ARDS with additional potential to reduce late SARS-CoV-2 complications related to immune-thrombotic events that persist during long COVID. Significance: Severe acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection manifests as uncontrolled tissue inflammation and systemic thrombosis with high mortality. Anti-viral drugs and monoclonal antibodies reduce COVID-19 severity if administered early, but treatments for later stage immuno-thrombosis are limited. Serine protease inhibitors (SERPINS) regulate thrombotic, thrombolytic and complement pathways. We investigate here systemic treatment with purified poxvirus-derived PEGSerp-1 as a therapeutic for immuno-thrombotic complications in viral ARDS. PEGSerp-1 treatment in two mouse-adapted SARS-CoV-2 models (C57Bl/6 and BALB/c) significantly reduced lung and heart inflammation and improved clinical outcomes, with sequential changes in thrombolytic (uPAR) and complement expression. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for immune-thrombotic complications in severe viral ARDS and has potential benefit for long COVID.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.09.507363v1" target="_blank">Treatment with anti-inflammatory viral serpin modulates immuno-thrombotic responses and improves outcomes in SARS-CoV-2 infected mice</a>
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</div></li>
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<li><strong>What is the impact of the COVID-19 pandemic epoch on IPD (Inpatient Department) hospital admissions in India- A 41months comparative, quantitative, deductive Cross-Sectional Research Study?</strong> -
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Abstract - The inpatient department or IPD is the dedicated unit of a hospital/healthcare facility for admitting patients from the OPD (outpatient department), ED (emergency department), or a referred patient usually from lower facilities for a planned care/procedure, for special medical problems that necessitate suitable care and consideration. The index case of SARS-CoV-2 virus infection in India was first suspected (based on clinical grounds) on 27th January 2020, an assumed case of covid-19 in Kerala with a current voyage history of Wuhan, china which was subsequently affirmed as SARS-CoV-2 virus infection positive case by the NIV (National Institute of Virology) situated at Pune in Maharashtra, on January 30th, 2020 as positive for COVID-19. As per the constitution of India Health is a subject matter of state, hence different states had reserved different percentages of beds in pre-existing health facilities for COVID-19 IPD patients, for example, the Delhi government had reserved 50% of pre-existing ICU (intensive care unit) and ward beds for COVID-19 IPD patient’s. Besides the other factors such as fear etc, mentioned above this new arrangement of hospital care delivery and prioritization of needs of COVID-19 patients may have resulted in the general cancellations of other IPD patients elective procedures leading to a reduced IPD number of patients with diseases other than COVID-19, as priority was shifted to COVID-19 admitted patient’s and cases. The first author researcher of this study has found unusual prevalence in the figure of IPD (Inpatient Department) hospital admissions during his normal course of duties at health centres throughout the current ongoing COVID-19(coronavirus disease-2019) era. To know about the real scenario a good sample size is a requirement for any epidemiological study. Hence this deductive study was done to confirm that, does the COVID-19 era have affected the number of IPD hospital admissions (positively or negatively). This study was started and designed to get an answer to the above question. The aim of this 41months comparative, quantitative, deductive, Cross-Sectional Research Study is to assess the direct impacts of COVID-19 on the number of IPD hospital admissions in India (other than COVID-19), across all public/private/rural/urban health facilities of 36 states and union territories registered on HMIS (Health Management Information System) of Ministry of Health and Family Welfare (MoHFW), Government of India on a cumulative basis. For the 17 months (2020-2021) COVID-19 pandemic epoch, the total mean number of IPD admissions was 5387311 compared to the total mean7435770 numbers of IPD admission for the previous pre-pandemic 2 years (2018-2019). The total mean number of IPD admission decreased by 2048459 numbers during the COVID-19 pandemic epoch i.e.27.55% decrease in IPD hospital admission observed during COVID-19. This research study revealed that there is a significant decrease in IPD hospital admissions for various medical conditions other than COVID-19 during the COVID-19 pandemic epoch which is a matter of concern for policy and decision-makers. A huge number of dead bodies were found floating in the sacred holy rivers of India (especially in the states of Bihar and Uttar Pradesh) during the ongoing COVID-19 epoch. Now it is quite possible that these dead bodies are of people with serious conditions other then COVID-19 who failed to get IPD admissions for treatment and died subsequently without treatment.
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🖺 Full Text HTML: <a href="https://osf.io/tqehr/" target="_blank">What is the impact of the COVID-19 pandemic epoch on IPD (Inpatient Department) hospital admissions in India- A 41months comparative, quantitative, deductive Cross-Sectional Research Study?</a>
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<li><strong>Real-world Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the United States</strong> -
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Background Sotrovimab, a recombinant human monoclonal antibody (mAb) against SARS-CoV-2 had US FDA Emergency Use Authorization (EUA) for the treatment of high-risk outpatients with mild-to-moderate COVID-19 from May 26, 2021, to April 5, 2022. The study objective was to evaluate the real-world effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality during the time period when the prevalence of circulating SARS-CoV-2 variants was changing between Delta and Omicron sub-lineages in the US. Methods A retrospective analysis was conducted on de-identified claims data for 1,530,501 patients diagnosed with COVID-19 (ICD-10: U07.1) from September 1, 2021, to April 30, 2022, in the FAIR Health National Private Insurance Claims (FH NPIC®) database. Patients meeting EUA high-risk criteria were identified via pre-specified ICD-10-CM diagnoses in records ≤24 months prior to their first COVID-19 diagnosis and divided into two cohorts based on claimed procedural codes: treated with sotrovimab (″sotrovimab″) and not treated with a mAb (″no mAb″). All-cause hospitalizations and facility-reported all-cause mortality within 30 days of diagnosis (″30-day hospitalization or mortality″) were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality among those treated with sotrovimab compared with those not treated with a mAb. Results Of the high-risk COVID-19 patients identified, 15,633 were treated with sotrovimab and 1,514,868 were not treated with a mAb. Compared with the no mAb cohort, the sotrovimab cohort was older and had a higher proportion of patients across the majority of high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8,167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, high-risk COVID-19 patients treated with sotrovimab had a 55% relative risk reduction of 30-day hospitalization or mortality (RR: 0.45, 95% CI: 0.41,0.49) and an 85% relative risk reduction of 30-day mortality (RR: 0.15, 95% CI: 0.08, 0.29) compared with high-risk patients not treated with a mAb. From September 2021 to April 2022, sotrovimab maintained clinical effectiveness with relative risk reductions of 30-day hospitalization or mortality ranging from 46% to 71%. Stratifying by high-risk condition, sotrovimab-treated patients exhibited statistically significant relative risk reductions of 30-day hospitalization or mortality compared with the no mAb cohort across all high-risk conditions (P<0.0001), ranging from 44% among pregnant women to 70% among patients 65 years and older. Conclusion In this large, US real-world, observational study of high-risk COVID-19 patients with reported diagnosis between September 2021 and April 2022 during the Delta and early Omicron variant waves, treatment with sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and facility-reported mortality compared with no mAb treatment. Sotrovimab clinical effectiveness persisted throughout the months when Delta and early Omicron sub-lineages were the predominant circulating variants in the US, though there was an uncertain RR estimate in April 2022 with wide confidence intervals due to the small sample size. Sotrovimab clinical effectiveness also persisted among all high-risk subgroups assessed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.07.22279497v1" target="_blank">Real-world Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the United States</a>
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<li><strong>Large-scale diagnostic assessment in first-year university students: pre- and trans-pandemic comparison</strong> -
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COVID-19 has disrupted higher education globally, and there is scarce information about the “learning loss” in university students that continued educational activities throughout the crisis. The goal of this study was to compare the scores in a large-scale knowledge diagnostic exam applied to students admitted to the university, before and during the pandemic. Research design was quasi-experimental with static group comparisons, taking advantage of the pandemic “natural experiment”, to assess knowledge in students admitted to the National Autonomous University of Mexico. The same instruments were applied to both cohorts to decrease instrumentation threat to validity. The 2018 test was a paper-and-pencil exam, the 2020 exam was applied online. 35,821 Students were evaluated in 2018 and 41,909 in 2020. The knowledge scores were 2 to 5% higher in the trans-pandemic assessment, except in the Spanish dimension where scores were 2% lower. Reliability and point biserial correlation coefficients were higher in the 2020 application. There was no documented learning loss in this large student population, with an increase in knowledge in the pandemic cohort. Some influence in scores due to the online testing modality can’t be ruled out. Longitudinal follow-up is required to continue evaluating the impact of the pandemic in learning.
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🖺 Full Text HTML: <a href="https://edarxiv.org/pxuh3/" target="_blank">Large-scale diagnostic assessment in first-year university students: pre- and trans-pandemic comparison</a>
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<li><strong>Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</strong> -
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Observational studies are being used more and more in psychology and medicine since they provide a wealth of data for real-world issues. Their biggest drawback is the lack of falsification due to the control mechanisms of control conditions being unavailable. However, the Covid-19 pandemic and the isolation policies related to it have provided an environment in which researchers can use natural experimental design to establish causal pathways in phenomena. Here we demonstrate how Covid-19-related changes can be used to investigate causal effects behind Home Advantage (HA), a robust phenomenon in which sport teams are more successful when they play in front of their fans. HA theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. Covid-19 has provided the perfect control condition for disentangling the causal links of the HA as sport teams have played at home but without the presence of fans. Using our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously instead of in isolation as was previously the case, we demonstrate how Covid-19 enables us to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, our paper also provides information about the practical implementation of mediation and moderated mediation mixed-effects models in the Bayesian framework. Similar implementations can be adapted in other medical and social science fields.
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🖺 Full Text HTML: <a href="https://osf.io/vz7de/" target="_blank">Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</a>
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<li><strong>Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.</strong> -
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Background: Secondary infection (SI) diagnosis in COVID-19 is challenging, due to overlapping clinical presentations, practical limitations in obtaining samples from the lower respiratory tract (LRT), and low sensitivity of microbiologic cultures. Research Question: Can metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) help diagnose SIs complicating COVID-19? Study Design and Methods: We enrolled 42 inpatients with COVID-19 classified as microbiologically-confirmed SI (Micro-SI, n=8), clinically-diagnosed SI (Clinical-SI, n=13, i.e. empiric antimicrobials), or no clinical suspicion for SI (No-Suspected-SI, n=21) at time of enrollment. From baseline and follow-up plasma samples (days 5 and 10 post-enrollment), we quantified mcfDNA for all detected microbes by mcfDNA sequencing and measured nine host-response biomarkers. From LRT samples among intubated subjects, we quantified bacterial burden with 16S rRNA gene quantitative PCR. Results: We performed mcfDNA-Seq in 82 plasma samples. Sequencing was successful in 60/82 (73.2%) samples, which had significantly lower levels of human cfDNA than failed samples (p<0.0001). McfDNA detection was significantly higher in Micro-SI (15/16 [94%]) compared to Clinical-SI samples (8/14 [57%], p=0.03), and unexpectedly common in No-Suspected-SI samples (25/30 [83%]), similar to detection rate in Micro-SI. We detected culture-concordant mcfDNA species in 13/16 Micro-SI samples (81%) and mcfDNA levels tracked with SI outcome (resolution or persistence) under antibiotic therapy. McfDNA levels correlated significantly with LRT bacterial burden (r=0.74, p=0.02) as well as plasma biomarkers of host response (white blood cell count, IL-6, IL-8, and SPD, all p<0.05). Baseline mcfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p=0.03). Interpretation: High circulating levels of mcfDNA in a substantial proportion of patients with COVID-19 without clinical suspicion for SI suggest that SIs may often remain undiagnosed. McfDNA-Seq, when clinically available, can offer a non-invasive diagnostic tool for pathogen identification, with prognostic value on host inflammatory response and clinical outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279790v1" target="_blank">Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA.</a>
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<li><strong>A phase 3, randomised, double-blind, placebo-controlled clinical trial for adult evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine (ABDALA-3 Study).</strong> -
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Background: The pandemic of COVID-19 raised the urgent need of safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 mcg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48290 subjects were included (24144 and 21146 in the placebo and Abdala groups, respectively). The product was well tolerated. No severe adverse events with demonstrated cause-effect relationship attributable to vaccine were reported. The incidence of adverse reactions in the placebo and Abdala vaccine arms were 446/24144 (1.9%) and 615/24146 (2.5%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 hours. The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). In the case of mild/moderate disease the vaccine efficacy was 91.96% (84.69-95.78) and 94.46% (58.52-99.28) for the severe forms (serious/critical disease). There were five critical patients (of which four died), all in the placebo group, indicating that Abdala vaccine efficacy for both conditions was of 100%. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.08.22279690v1" target="_blank">A phase 3, randomised, double-blind, placebo-controlled clinical trial for adult evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine (ABDALA-3 Study).</a>
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<li><strong>LEAF- 4L6715 enhances oxygenation in patients with acute respiratory distress syndrome (ARDS) due to severe COVID-19: Final results of a phase I/II clinical trial</strong> -
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LEAF-4L6715 is a liposomal formulation encapsulating transcrocetin (TC) developed to enhance the diffusion of oxygen in the body. Here, we report the final results of the phase I/II clinical trial (NCT04378920; EUDRACT2020-001393-30) initiated to identify an optimal regimen and to assess the activity of TC in the context of acute respiratory distress syndrome (ARDS). More specifically, LEAF-4L6715 was developed to treat patients with ARDS due to severe SARS-CoV-2 infection who have a ratio of partial arterial pressure to inspired fraction of oxygen (PaO2/FiO2 ratio) <200 treated with artificial ventilation support in an intensive care unit. A total of 37 patients were treated (across 6 dosing cohorts) with LEAF-4L6715 given as an intravenous infusion for over 90 minutes. The dose of LEAF-4L6715 was increased until the transaminase levels were elevated and 4 grade 3 events occurred among 8 patients. The recommended dosage was determined to be a fixed concentration of 300 mg administered every 12 hours. An improvement in the PaO2/FiO2 ratio and SOFA score was observed. The overall 28-day survival rate of 81%. This study identified the recommended dose for LEAF-4L6715 and the dose-limiting toxicity and showed an overall favorable risk/benefit profile. These preliminary findings are promising for the activity of LEAF-4L6715 but will require confirmation in a randomized phase III trial.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.07.22279668v1" target="_blank">LEAF- 4L6715 enhances oxygenation in patients with acute respiratory distress syndrome (ARDS) due to severe COVID-19: Final results of a phase I/II clinical trial</a>
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<li><strong>Effectiveness of incentivized peer referral to increase enrollment in a community-based chlamydia screening and treatment study among young Black men</strong> -
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Abstract Purpose: Incentivized peer referral (IPR) has been shown to be an effective method of recruitment for men who have sex with men but has not been studied extensively in men who have sex with women (MSW), particularly among Black MSW. We aimed to determine if IPR was more effective than uncompensated peer referral for recruiting young Black men into a community STI screening study. Methods: We used data from the Check It study, a chlamydia (Ct) screening and treatment program for young Black men ages 15-26 in New Orleans, LA. Enrollment was compared before and after IPR was implemented using Multiple Series Analysis (MTSA). IPR was introduced to increase recruitment that had been severely diminished because of the COVID-19 shutdown. Results: Of 1527 men enrolled, 1399 (91.6%) were enrolled pre-IPR and 128 (8.4%) were enrolled post-IPR. The percentage of men referred by a friend or peer was higher in the post-IPR period than in the pre-IPR period (45.7% vs. 19.7%, p<0.001). Post-pandemic, we observed a statistically significant increase of 2.007 more recruitments (p=0.044, 95% CI (0.0515, 3.964)) at the start of the post-IPR era, compared to the pre-IPR era. Overall, we also observed a trending increase in recruitments in the IPR era relative to the pre-IPR era (0.0174 recruitments/week, p=0.285, 95% CI (-0.0146, 0.0493)) with less recruitment decay in the post-IPR compared to pre-IPR. Conclusions: IPR may be an effective means of engaging young Black men in community based STI research and prevention programs, particularly when clinic access is limited.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279725v1" target="_blank">Effectiveness of incentivized peer referral to increase enrollment in a community-based chlamydia screening and treatment study among young Black men</a>
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<li><strong>THE EFFECT OF THE MEASLES, MUMPS AND RUBELLA VACCINE ON INNATE AND ADAPTIVE IMMUNE RESPONSES IN PERSONS RECEIVING A SARS-COV-2 mRNA VACCINE. A SUB-STUDY OF THE CROWN CORONATION TRIAL</strong> -
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ABSTRACT Vaccination elicits a complex combination of immune responses. Immune memory formation is observed not only in the antibody responses of B-cells, but also in the T-cell response. Moreover, some live attenuated vaccines such as measles-containing vaccines can induces heterologous protection, likely through induction of memory characteristics in the innate immune response. Little is known about the immunological interaction that may occur when different vaccines are administered soon after one another, especially in relation to the novel COVID-19 vaccines. The aim of this study was to compare the innate and adaptive immune responses between persons randomized to receive either a MMR or a placebo (0.9% NaCl) injection prior to their SARS-CoV-2 mRNA vaccination. We compared: i) the cytokine and chemokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10, IL-17, IL-22, interferon [IFN]-α and IFN-γ) after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) with heterologous stimuli (severe acute respiratory syndrome coronavirus [SARS-CoV]-2, measles mumps and rubella [MMR] vaccine, Toll-like receptor [TLR]-3 ligand, TLR-7/8 ligand, or TLR-4 ligand), and ii) the SARS-CoV-2 neutralizing antibody responses. Ninety-five participants in the CROWN CORONATION trial (NCT04333732; a randomized control trial comparing MMR to placebo for prevention of COVID-19) agreed to an additional single blood sample collection for this immunological study. Samples were collected around 196 (SD 22) days after administration of MMR or placebo, and around 105 (SD 27) days after their second SARS-CoV-2 mRNA vaccine injection. Twenty-four percent of participants were older than fifty and sixty-seven percent were female. The median TNF-α response to stimulation with MMR was 8315.3 pg/mL in the MMR group and 4340.5 pg/mL in the placebo group; adjusted median difference (95% CI) 3012.5 (-4734.1; -323.5); p=0.017. No other significant differences were noted in the cytokine and chemokine responses between treatment groups. The SARS-CoV-2 neutralization assay geometric mean (SD) IC50 in the MMR group was 507.6 (2.6) and in the placebo group was 515.7 (2.2); ratio of geometric means (95% CI) 1.0 (0.7; 1.5). Pre-exposure to MMR vaccine was generally not associated with changes in cytokine and chemokine responses of stimulated PBMCs at 105 (27) days after SARS-CoV-2 mRNA vaccination. MMR vaccination led only to an increase of TNF-α production in response to an additional ex-vivo stimulation with the MMR vaccine. The SARS-CoV-2 neutralization IC50 values did not differ between MMR and placebo groups. Further studies using a repeated measures design would be better suited to explore or rule-out any short-lived vaccine response and vaccine-vaccine immunological interaction.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279771v1" target="_blank">THE EFFECT OF THE MEASLES, MUMPS AND RUBELLA VACCINE ON INNATE AND ADAPTIVE IMMUNE RESPONSES IN PERSONS RECEIVING A SARS-COV-2 mRNA VACCINE. A SUB-STUDY OF THE CROWN CORONATION TRIAL</a>
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<li><strong>SARS-CoV-2 Serosurveys: How antigen, isotype and threshold choices affect the outcome</strong> -
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Background: Evaluating the performance of SARS-CoV-2 serological assays and clearly articulating the utility of selected antigen, isotypes and thresholds is crucial to understanding the prevalence of infection within selected communities. Methods: This cross-sectional study, implemented in 2020, screened PCR-confirmed COVID-19 patients (n=86), banked pre-pandemic and negative donors (n=96), health care workers and family members (n=552), and university employees (n=327) for anti-SARS-CoV-2 receptor-binding domain (RBD), trimeric spike protein (S), and nucleocapsid protein (N) IgG and IgA antibodies with a laboratory developed Enzyme-Linked Immunosorbent Assay (ELISA) and tested how antigen, isotype and threshold choices affected the seroprevalence. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen/isotype combination; and (iii) the maximal Youden index. Results: We found vastly different seroprevalence estimates depending on selected antigens, isotypes and the applied threshold method, ranging from 0.0% to 85.4%. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%. Conclusions: This study revealed the importance of evaluating serosurvey tools for antigen, isotype, and threshold-specific sensitivity and specificity, in order to interpret qualitative serosurvey outcomes reliably and consistently across studies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279787v1" target="_blank">SARS-CoV-2 Serosurveys: How antigen, isotype and threshold choices affect the outcome</a>
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<li><strong>Population Normalization in SARS-CoV-2 Wastewater-Based Epidemiology: Implications from Statewide Wastewater Monitoring in Missouri</strong> -
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The primary objective of this study was to identify a universal wastewater biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology (WBE). A total of 2,624 wastewater samples (41 weeks) were collected weekly during May 2021- April 2022 from 64 wastewater facilities across Missouri, U.S. Three wastewater biomarkers, caffeine and its metabolite, paraxanthine, and pepper mild mottle virus (PMMoV), were compared for the population normalization effectiveness for wastewater SARS-CoV-2 surveillance. Paraxanthine had the lowest temporal variation and strongest relationship between population compared to caffeine and PMMoV. This result was confirmed by data from ten different Wisconsin WWTPs with gradients in population sizes, indicating paraxanthine is a promising biomarker of the real-time population across a large geographical region. The estimated real-time population was directly compared against the population patterns with human movement mobility data. Of the three biomarkers, population normalization by paraxanthine significantly strengthened the relationship between wastewater SARS-CoV-2 viral load and COVID-19 incidence rate the most (40 out of 61 sewersheds). Caffeine could be a promising population biomarker for regions where no significant exogenous caffeine sources (e.g., discharges from food industries) exist. In contrast, PMMoV showed the highest variability over time, and therefore reduced the strength of the relationship between sewage SARS-CoV-2 viral load and the COVID-19 incidence rate, as compared to wastewater data without population normalization and the population normalized by either recent Census population or the population estimated based on the number of residential connections and average household size for that municipality from the Census. Overall, the findings of this long-term surveillance study concluded that the paraxanthine has the best performance as a biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.08.22279459v1" target="_blank">Population Normalization in SARS-CoV-2 Wastewater-Based Epidemiology: Implications from Statewide Wastewater Monitoring in Missouri</a>
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<li><strong>Nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.</strong> -
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Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods Plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralising titres against all variants. Of 180 with complete data, 160 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279759v1" target="_blank">Nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.</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>Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Universitas Padjadjaran; Udayana University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-1 on D0; Biological: SCTV01E-1 on D28; Biological: SCTV01E-1 on D150; Biological: SCTV01E on D0; Biological: SCTV01E on D28; Biological: SCTV01E on D150; Biological: SCTV01E-1 on D120; Biological: SCTV01E on D120<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Diagnostic Test: the LIT test<br/><b>Sponsors</b>: Gazi University; Oxford MediStress<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>Efficacy and Safety of ES16001 in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ES16001 40 mg; Drug: ES16001 80 mg; Drug: ES16001 160 mg; Drug: Placebo<br/><b>Sponsor</b>: Genencell Co. Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID)</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Behavioral: Personalized multidisciplinary day-hospital intervention<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Comirnaty®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Vaxzevria®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19</strong> - <b>Conditions</b>: Long COVID; COVID-19<br/><b>Intervention</b>: Behavioral: Cardiac Rehabilitation<br/><b>Sponsor</b>: University of California, San Francisco<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>The Impact of a Web-based Psychoeducation Programme With a Motivational AI Chatbot on Covid-19 Vaccine Hesitancy</strong> - <b>Conditions</b>: Vaccine Hesitancy; COVID-19<br/><b>Interventions</b>: Behavioral: AI-driven Vaccine Communicator; Behavioral: Self-learning of COVID-19 vaccine knowledge<br/><b>Sponsor</b>: The Hong Kong Polytechnic University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Motivation, Syringe Exchange, and COVID-19</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Connect2Test<br/><b>Sponsors</b>: University of Oregon; National Institute on Drug Abuse (NIDA)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rehabilitation Therapy for Post COVID 19 Chronic Fatigue Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: intensive combined rehabilitation therapy<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>HRQOL of Life After ECMO Due to COVID-19.</strong> - <b>Conditions</b>: ARDS; COVID-19 Pneumonia; Extracorporeal Membrane Oxygenation<br/><b>Intervention</b>: Other: Phone Interview<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The FDA-approved drug Auranofin has a dual inhibitory effect on SARS-CoV-2 entry and NF-κB signaling</strong> - Patients with severe COVID-19 exhibit an altered immune response that fails to control viral spread and suffer from exacerbated inflammatory response, which eventually can lead to death. A major challenge is to develop an effective treatment for COVID-19. NF-κB is a major player in the innate immunity and inflammatory process. By a high-throughput screening approach, we identified FDA-approved compounds that inhibit the NF-κB pathway and thus dampen inflammation. Among these, we show that…</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>TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide outbreak, known as coronavirus disease 2019 (COVID-19). Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to COVID-19. We previously reported that TEMPOL, a small molecule stable nitroxide, inactivated the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 by causing the oxidative degradation of its iron-sulfur cofactors. Here, we demonstrate that TEMPOL is effective 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>Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants</strong> - The molecular manifestations of host cells responding to SARS-CoV-2 and its evolving variants infection are vastly different across studying models and conditions, imposing challenges for host-based antiviral drug discovery. Based on the postulation that antiviral drugs tend to reverse the global host gene expression induced by viral infection, we retrospectively evaluated hundreds of signatures derived from 1700 published host transcriptomic profiles of SARS/MERS/SARS-CoV-2 infection using an…</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>Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization</strong> - The ability of serum antibody to protect against pathogens arises from the interplay of antigen-specific B cell clones of different affinities and fine specificities. These cellular dynamics are ultimately responsible for serum-level phenomena such as antibody imprinting or “Original Antigenic Sin” (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells that responded to a stimulus upon exposure to related antigens. Imprinting/OAS is thought to pose a…</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>Computational screening for investigating the synergistic regulatory potential of drugs and phytochemicals in combination with 2-deoxy-D-glucose against SARS-CoV-2</strong> - COVID-19 disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) in March 2020. Since then, the SARS-CoV-2 virus has impacted millions of lives worldwide. Various preclinical and clinical trials on the treatment of COVID-19 disease have revealed that the drugs that work in combination are more likely to reduce reinfection and multi-organ failure. Considering the combination drug therapy, herein, we…</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>Deciphering inhibitory mechanism of coronavirus replication through host miRNAs-RNA-dependent RNA polymerase interactome</strong> - Despite what we know so far, Covid-19, caused by SARS-CoV-2 virus, remains a pandemic that still require urgent healthcare intervention. The frequent mutations of the SARS-CoV-2 virus has rendered disease control with vaccines and antiviral drugs quite challenging, with newer variants surfacing constantly. There is therefore the need for newer, effective and efficacious drugs against coronaviruses. Considering the central role of RNA dependent, RNA polymerase (RdRp) as an enzyme necessary for…</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>Nanoemulsion as an Effective Inhibitor of Biofilm-forming Bacterial Associated Drug Resistance: An Insight into COVID Based Nosocomial Infections</strong> - Antibiotic overuse has resulted in the microevolution of drug-tolerant bacteria. Understandably it has become one of the most significant obstacles of the current century for scientists and researchers to overcome. Bacteria have a tendency to form biofilm as a survival mechanism. Biofilm producing microorganism become far more resistant to antimicrobial agents and their tolerance to drugs also increases. Prevention of biofilm development and curbing the virulency factors of these multi drug…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mechanisms of Coronavirus Genome Stability As Potential Targets for Antiviral Drugs</strong> - The COVID-19 pandemic has made it necessary to create antivirals active against the SARS-CoV-2 coronavirus. One of the widely used strategies to fight off viral infections is the use of modified nucleoside analogues that inhibit viral replication by incorporating DNA or RNA into the growing chain, thus stopping its synthesis. The difficulty of using this method of treatment in the case of SARS-CoV-2 is that coronaviruses have an effective mechanism for maintaining genome stability. Its central…</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>Optimal COVID-19 therapeutic candidate discovery using the CANDO platform</strong> - The worldwide outbreak of SARS-CoV-2 in early 2020 caused numerous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two…</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>C</em> <em>apsicum</em> fruits as functional ingredients with antimicrobial activity: an emphasis on mechanisms of action</strong> - Capsicum spp. fruits (CFs) are a basic ingredient in the diet and have been used as active ingredients in the pharmaceutical, cosmetic, and food products, due to their antioxidant, anti-inflammatory, antiseptic, and antimicrobial properties. The antimicrobial activity is the most studied property due to its effectiveness against pathogenic species, however, few studies have focused on the mechanisms of action involved. Therefore, this review discusses the effects generated by the CFs compounds…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication</strong> - Cases of coronavirus disease 2019 (COVID-19) have been reported worldwide. However, one epidemiological report has claimed a lower incidence of the disease in people living at high altitude (>2,500 m), proposing the hypothesis that adaptation to hypoxia may prove to be advantageous with respect to SARS-CoV-2 infection. This publication was initially greeted with skepticism, because social, genetic, or environmental parametric variables could underlie a difference in susceptibility to the virus…</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 vaccination in advanced skin cancer patients receiving systemic anticancer treatment: A prospective singlecenter study investigating seroconversion rates</strong> - CONCLUSION AND RELEVANCE: Rate of anti-SARS-CoV-2-S IgG seroconversion in advanced skin cancer patients under systemic anticancer treatment after complete COVID-19 vaccination is comparable to other cancer entities. An impaired serological response was observed in patients who were immunocompromised due to concomitant diseases or previous chemotherapies. Immunosuppressive comedication due to severe adverse events of ICI did not impair the serological response to COVID-19 vaccination.</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>Targeted escape of SARS-CoV-2 <em>in vitro</em> from monoclonal antibody S309, the precursor of sotrovimab</strong> - Class 1 and 2 monoclonal antibodies inhibit SARS-CoV-2 entry by blocking the interaction of the viral receptor-binding domain with angiotensin-converting enzyme 2 (ACE2), while class 3 antibodies target a highly conserved epitope outside the ACE2 binding site. We aimed to investigate the plasticity of the spike protein by propagating wild-type SARS-CoV-2 in the presence of class 3 antibody S309. After 12 weeks, we obtained a viral strain that was completely resistant to inhibition by S309, due…</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>Putative COVID-19 therapies imatinib, lopinavir, ritonavir, and ivermectin cause hair cell damage: A targeted screen in the zebrafish lateral line</strong> - The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials. We used the zebrafish lateral line, an established…</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>Down-regulation of RdRp complex and activated immune response due to increased arsenic level leads to decreased corona virus replication</strong> - Corona virus is pandemic and responsible for more than 5.6 million deaths. It was observed that its severity was reported in varied ways in different countries and even in different states of India. This variation was critically evaluated in the area with high contamination of Arsenic (As) to understand the arsenic toxicity and Covid epidemiology and associated health effects in the human population. It was reported that the area with low arsenic contamination has a very high incidence rate of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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