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186 lines
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<title>25 May, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model</strong> -
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RSV and SARS-CoV-2 are prone to co-infection with other respiratory viruses. In this study, we use RSV/SARS-CoV-2 co-infection to evaluate changes to clinical disease and viral replication in vivo. To consider the severity of RSV infection, effect of sequential infection, and the impact of infection timing, mice were co-infected with varying doses and timing. Compared with a single infection of RSV or SARS-CoV-2, the co-infection of RSV/SARS-CoV-2 and the primary infection of RSV followed by SARS-CoV-2 results in protection from SARS-CoV-2-induced clinical disease and reduces SARS-CoV-2 replication. Co-infection also augmented RSV replication at early timepoints with only the low dose. Additionally, the sequential infection of RSV followed by SARS-CoV-2 led to improved RSV clearance regardless of viral load. However, SARS-CoV-2 infection followed by RSV results in enhanced SARS-CoV-2-induced disease while protecting from RSV-induced disease. SARS-CoV-2/RSV sequential infection also reduced RSV replication in the lung tissue, regardless of viral load. Collectively, these data suggest that RSV and SARS-CoV-2 co-infection may afford protection from or enhancement of disease based on variation in infection timing, viral infection order, and/or viral dose. In the pediatric population, understanding these infection dynamics will be critical to treat patients and mitigate disease outcomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.24.542043v1" target="_blank">The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model</a>
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</div></li>
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<li><strong>Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants</strong> -
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The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics - such as vaccination status, exposure history and age - we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.17.23290105v1" target="_blank">Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants</a>
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</div></li>
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<li><strong>Primary Care Post-COVID syndrome Diagnosis and Referral Coding</strong> -
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Introduction - Guidelines for diagnosing and managing Post-COVID syndrome have been rapidly developed. Consistency of the application of these guidelines in primary care is unknown. Electronic health records provide an opportunity to review the use of codes relating to Post-COVID syndrome. This paper explores the use of primary care records as a surrogate uptake measure for NICEs rapid guideline managing the long-term effects of COVID-19 by measuring the use of Post-COVID syndrome diagnosis and referral codes in the pathway. Method - With the approval of NHS England we used routine clinical data from the OpenSafely-EMIS/-TPP platforms. Counts of Post-COVID syndrome diagnosis and referral codes were generated from a cohort of all adults, establishing numbers of diagnoses and referrals following diagnosis. The relationship between Post-COVID syndrome diagnosis and referral codes was explored with reference to NICEs rapid guideline. Results - Of over 45 million patients, 69,220 (0.15%) had a Post-COVID syndrome diagnostic code, and 67,741 (0.15%) had a referral code. 78% of referral codes did not have an associated diagnosis code. 79% of diagnosis codes had no subsequent referral code. Only 18,633 (0.04%) had both. There were higher rates of both diagnosis and referral in those who were more deprived, female and some ethnic groups. Discussion - This study demonstrates variation in diagnosis and referral coding rates for Post-COVID syndrome across different patient groups. The results, with limited crossover of referral and diagnostic codes, suggest only one type of code is usually recorded. Recording one code limits the use of routine data for monitoring Post-COVID syndrome diagnosis and management, but suggests several areas for improvement in coding. Post-COVID syndrome coding, particularly diagnosis coding, needs to improve before administrators and researchers can use it to evaluate care pathways.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.23.23289798v1" target="_blank">Primary Care Post-COVID syndrome Diagnosis and Referral Coding</a>
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<li><strong>Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors, the impact of the COVID-19 pandemic and possible opportunities for intervention</strong> -
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In recent years, hospital managers have reported increasing numbers of psychiatric hospital admissions in the Western Cape Province of South Africa, driven by poverty and substance use. We aimed to examine this trend, and the impact of the COVID-19 pandemic, as well as assess factors associated with linkage to ambulatory services following hospital discharge and repeat psychiatric admissions. Using electronic health data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape public sector from 2015 to 2022 were analyzed, stratified by hospital level. Mixed effects logistic regression was used in this cohort study to determine the factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days. We found that psychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion of diagnoses were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year before the admission. Male patients and those with substance use disorders were less likely to be successfully linked to outpatient services following discharge. Successful linkage was one of the most protective factors against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively. Improving linkage to ambulatory services by mental health patients post-discharge is likely to avert hospital readmissions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.17.23290107v1" target="_blank">Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors, the impact of the COVID-19 pandemic and possible opportunities for intervention</a>
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<li><strong>Posttraumatic stress disorder symptom trajectories in a 16-month COVID-19 pandemic period</strong> -
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In the aftermath of mass trauma, posttraumatic stress disorder (PTSD) symptoms follow prototypical trajectories of resilience, recovery, or chronic distress. The coronavirus disease 2019 (COVID-19) pandemic represented an unheralded opportunity to better understand heterogeneous trajectories of PTSD symptoms across a prolonged period of social disruption and stress. We tracked the PTSD symptoms of trauma-exposed individuals in the U.S., sought to identify population-based variability in PTSD symptom trajectories, and understand what, if any, early pandemic experiences would predict their membership in one trajectory over others. As part of a large-scale longitudinal study of U.S. residents during the pandemic, participants who reported at least one potentially traumatic event in their lifetime (N = 1206) at Wave 1 (April 2020) were included in the current study. PTSD symptoms were assessed with the PTSD Checklist for DSM-5 at four time points extending to July 2021. Latent growth mixture modeling was used to identify heterogeneous symptom trajectories. Trajectory membership was regressed on baseline demographics and experiences from the early stage of the pandemic as measured by the Epidemic-Pandemic Impacts Inventory. Four trajectories (Resilient [73%], Recurring [13.3%], Recovering [8.3%], and Chronic [5.5%] were identified. Age, trauma load, and early pandemic experiences (emotional/physical health problems and positive changes) were each significant predictors of trajectory membership. Predictors primarily differentiated the Resilient from each of the other three trajectories. Distinct PTSD symptom trajectories during the COVID-19 pandemic point to the need for targeted efforts helping those at most risk for ongoing distress.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/wpjgm/" target="_blank">Posttraumatic stress disorder symptom trajectories in a 16-month COVID-19 pandemic period</a>
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<li><strong>Experiences, impacts and mental health functioning during a COVID-19 outbreak and lockdown: Data from a diverse New York City sample of college students</strong> -
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In March 2020, New York City (NYC) experienced an outbreak of coronavirus disease 2019 (COVID-19) which resulted in a 78-day mass confinement of all residents other than essential workers. The aims of the current study were to (1) document the breadth of COVID-19 experiences and their impacts on college students of a minority-serving academic institution in NYC; (2) explore associations between patterns of COVID-19 experiences and psychosocial functioning during the prolonged lockdown, and (3) explore sex and racial/ethnic differences in COVID-19-related experiences and mental health correlates. A total of 909 ethnically and racially diverse students completed an online survey in May 2020. Findings highlight significant impediments to multiple areas of students’ daily life during this period (i.e., home life, work life, social environment, and emotional and physical health) and a vast majority reported heightened symptoms of depression and generalized anxiety. These life disruptions were significantly related to poorer mental health. Moreover, those who reported the loss of a close friend or loved one from COVID-19 (17%) experienced significantly more psychological distress than counterparts with other types of infection-related histories. Nonetheless, the majority (96%) reported at least one positive experience since the pandemic began. Our findings add to a growing understanding of COVID-19 impacts on psychological health and contribute the important perspective of the North American epicenter of the pandemic during the time frame of this investigation. We discuss how the results may inform best practices to support students’ well-being and serve as a benchmark for future studies of US student populations facing COVID-19 and its aftermath.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/nyght/" target="_blank">Experiences, impacts and mental health functioning during a COVID-19 outbreak and lockdown: Data from a diverse New York City sample of college students</a>
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<li><strong>Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination: estimation and correction using a data augmentation model</strong> -
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Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iterative data augmentation. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.23.23290384v1" target="_blank">Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination: estimation and correction using a data augmentation model</a>
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<li><strong>Emotional overeating affected nine in ten female students during the COVID-19 University closure: A cross-sectional study in France</strong> -
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Objectives: To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress. Design: Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined. Participants: Sample of 302 female students from Rennes University, France. Main Outcome Measure: Frequencies of emotional overeating. Analysis: The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates. Results: Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting “Distress-Induced Overeating” positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse. Conclusion and Implications: Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.17.23290100v1" target="_blank">Emotional overeating affected nine in ten female students during the COVID-19 University closure: A cross-sectional study in France</a>
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<li><strong>Wastewater Surveillance for SARS-CoV-2 in an Atlanta, Georgia Jail: A study of the feasibility of wastewater monitoring and correlation of building wastewater and individual testing results.</strong> -
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Background Wastewater-based surveillance (WBS) on an institutional level was implemented during the COVID-19 pandemic, including carceral facilities. In this study of a mega-jail, we examined the relationship between COVID-19 diagnostic test results from jail residents and the PCR signal for SARS-CoV-2 detection in weekly samples of jail wastewater over a 28-week period. Methods This study in a Georgia Jail (average population ~2,700) was conducted October 2021-May 2022. Weekly on-site wastewater samples were collected (Moore Swabs) and tested for SARS-CoV-2 RNA using RTqPCR. The source of wastewater was identified using a tracer dye. The jail offered residents rapid antigen testing at entry. We conducted periodic mass screenings via RT-PCR of nasal swabs. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between the strength of the SARS-CoV-2 PCR signal (Ct value) in wastewater and the proportion of the jail population that tested positive for COVID-19. Results Overall, 3770 individual nasal specimens were collected; 3.4% were COVID-positive. Weekly diagnostic test positivity ranged from 0%-29.5%. Dye tests demonstrated that a single wastewater collection point was sufficiently representative of the jails aggregate viral load. Twenty-five wastewater samples were collected. RT-qPCR Ct values for wastewater samples with SARS-CoV-2 RNA ranged from 28.1-39.9. A strong inverse correlation was observed between diagnostic test positivity and Ct value (r= -0.67, p < 0.01). Conclusion WBS was shown to be an effective strategy for surveilling COVID-19 in a large jail. Strong partnerships with the jail administration are essential to the success of WBS surveillance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.17.23290000v1" target="_blank">Wastewater Surveillance for SARS-CoV-2 in an Atlanta, Georgia Jail: A study of the feasibility of wastewater monitoring and correlation of building wastewater and individual testing results.</a>
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<li><strong>Spatiotemporal Variations of “Triple-demic” Outbreaks of Respiratory Infections in the United States in the Post-COVID-19 Era</strong> -
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Objectives: The United States confronted a “triple-demic” of influenza, respiratory syncytial virus, and COVID-19 in the winter of 2022, resulting in increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze each epidemic and their co-occurrence in space and time to identify hotspots and provide insights for public health strategy. Methods: We used retrospective space-time scan statistics to retrospect the situation of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and then applied prospective space-time scan statistics to monitor spatiotemporal variations of each individual epidemic, respectively and collectively from October 2022 to February 2023. Results: Our analysis indicated that compared to the winter of 2021, COVID-19 cases decreased while influenza and RSV infections increased significantly during the winter of 2022. We revealed that a twin-demic high-risk cluster of influenza and COVID-19 but no triple-demic clusters emerged during the winter of 2021. We further identified a large high-risk cluster of triple-demic in the central US from late November, with COVID-19, influenza, and RSV having relative risks of 1.14, 1.90, and 1.59, respectively. The number of states at high risk for multiple-demic increased from 15 in October 2022 to 21 in January 2023. Conclusion: Our study provides a novel spatiotemporal perspective to explore and monitor the transmission patterns of the triple epidemic, which could inform public health authorities9 resource allocation to mitigate future outbreaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.23.23290387v1" target="_blank">Spatiotemporal Variations of “Triple-demic” Outbreaks of Respiratory Infections in the United States in the Post-COVID-19 Era</a>
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<li><strong>Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 Spike protein</strong> -
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Background: SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper- proinflammatory state involves activation of signaling by NF{kappa}B and ENaC, and expression of high levels of cytokines and chemokines. Post-infection inflammation may contribute to “Long COVID”, and there are also other long term consequences of acute severe COVID-19, which double or triple the chances of dying from any cause within a year. Enhanced signaling by NF{kappa}B and ENaC also marks the airway of patients suffering from cystic fibrosis, a lethal proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 Spike protein. Methods: This hypothesis was tested using the hTERT-transformed BCi-NS1.1 basal stem cell, previously derived from small airway epithelia, which were differentiated into a model of small airway epithelia on an air-liquid-interface (ALI). Cyclic AMP-activated CFTR chloride channel activity was measured using an Ussing Chamber. Cell surface-CFTR was labeled with the impermeant biotin method. Results: Exposure of differentiated airway epithelia to SARS-CoV-2 Spike protein resulted in loss of CFTR protein expression. As hypothesized, TNF/NF{kappa}B signaling was activated, based on increased protein expression of TRADD, the first intracellular adaptor for the TNF/TNFR1 complex, TNFR1, the TNF receptor, phosphorylated I{kappa}B, and the chemokine IL8. ENaC activity was also activated, based on specific changes in molecular weights for and {gamma}ENaC. Exposure of the epithelia to viral Spike protein suppressed cAMP-activated CFTR chloride channel activity. However, addition of 30 nM concentrations of cardiac glycoside drugs ouabain, digitoxin and digoxin, prevented loss of channel activity. ACE2 and CFTR were found to co-immunoprecipitate (co-IP) in both basal cells and epithelia, suggesting that the mechanism for Spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, Spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane, suggesting that failure of CFTR recovery from endosomal recycling might be a mechanism for Spike-dependent loss of CFTR. Conclusion: Based on experiments with this model of small airway epithelia, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by SARS-CoV-2 Spike protein, thus inducing a CFTR-null, cystic fibrosis-like clinical phenotype. Descriptions of COVID-19 in CF carriers with only one copy of wildtype CFTR suggest that this model-based conclusion might be consistent with patient-based experience.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.18.476803v3" target="_blank">Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 Spike protein</a>
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<li><strong>Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature</strong> -
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Background: The COVID-19 pandemic has led to an unprecedented amount of scientific publications, growing at a pace never seen before. Multiple living systematic reviews have been developed to assist professionals with up-to-date and trustworthy health information, but it is increasingly challenging for systematic reviewers to keep up with the evidence in electronic databases. We aimed to investigate deep learning-based machine learning algorithms to classify COVID-19 related publications to help scale-up the epidemiological curation process. Methods: In this retrospective study, five different pre-trained deep learning-based language models were fine-tuned on a dataset of 6,365 publications manually classified into two classes, three subclasses and 22 sub-subclasses relevant for epidemiological triage purposes. In a k-fold cross-validation setting, each standalone model was assessed on a classification task and compared against an ensemble, which takes the standalone model predictions as input and uses different strategies to infer the optimal article class. A ranking task was also considered, in which the model outputs a ranked list of sub-subclasses associated with the article. Results: The ensemble model significantly outperformed the standalone classifiers, achieving a F1-score of 89.2 at the class level of the classification task. The difference between the standalone and ensemble models increases at the sub-subclass level, where the ensemble reaches a micro F1-score of 70% against 67% for the best performing standalone model. For the ranking task, the ensemble obtained the highest recall@3, with a performance of 89%. Using an unanimity voting rule, the ensemble can provide predictions with higher confidence on a subset of the data, achieving detection of original papers with a F1-score up to 97% on a subset of 80% of the collection instead of 93% on the whole dataset. Conclusion: This study shows the potential of using deep learning language models to perform triage of COVID-19 references efficiently and support epidemiological curation and review. The ensemble consistently and significantly outperforms any standalone model. Fine-tuning the voting strategy thresholds is an interesting alternative to annotate a subset with higher predictive confidence.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.18.524571v2" target="_blank">Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature</a>
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<li><strong>ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface</strong> -
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Vaccines against SARS-CoV-2 have been proven to be an effective means of decreasing COVID-19 mortality, hospitalization rates, and transmission. One of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Using cryo-electron tomography and subtomogram averaging, we determined the native structures of the vaccine product expressed on cell surfaces in situ. We show that ChAdOx1-vectored vaccines expressing the Beta SARS-CoV-2 variant produce abundant native prefusion spikes predominantly in one-RBD-up conformation. Furthermore, the ChAdOx1 vectored HexaPro stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild-type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.22.541685v1" target="_blank">ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface</a>
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<li><strong>The impact of age and psychosocial factors on cognitive and auditory outcomes during the COVID-19 pandemic</strong> -
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Purpose: In March 2020, the UK government announced that people should isolate to reduce the spread of the virus that causes COVID-19. Outside a pandemic, psychosocial factors, such as socialisation and mental health, may impact the relationship between hearing loss and increased dementia risk. We aim to report the impact of psychosocial factors, including social isolation, depression, and engagement in activities, on hearing and cognitive function in younger and older adults during the COVID-19 pandemic. Method: An online survey and experiment assessed self-reported psychosocial factors, self-reported hearing ability and speech-in-noise perception, and cognition. Data were collected between June 2020 and February 2021. Older (N = 112, MAGE = 70.08) and younger (N = 121, MAGE = 20.52) monolingual speakers of English, without any language or neurological disorders participated. Multiple linear regression models were employed to investigate hypothesised associations between psychosocial factors, and hearing and cognition, in older and younger adults. Results: Multiple regression analyses indicated that older adults displayed poorer speech-in-noise perception and poorer performance on one of four cognitive tasks, compared to younger adults; and increased depression was associated with poorer subjective hearing. Other psychosocial factors did not significantly predict hearing or cognitive function. Conclusions: Data suggest that self-reported hearing and depression are related. This conclusion is important for understanding the associations between hearing loss and cognitive decline in the long-term, as both hearing loss and depression are risk factors for dementia.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rqfjy/" target="_blank">The impact of age and psychosocial factors on cognitive and auditory outcomes during the COVID-19 pandemic</a>
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<li><strong>Smaller preferred interpersonal distance for joint versus parallel action</strong> -
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During social interaction, humans prefer to keep a certain distance between themselves and other individuals. This preferred “interpersonal distance” (IPD) is known to be sensitive to social context, and in the present study we aimed to further investigate the extent to which IPD is affected by the specific type of social interaction. In particular, we focused on the contrast between joint actions, where two or more individuals coordinate their actions in space and time to achieve a shared goal, and parallel actions, where individuals act alongside each other but individually. We predicted that joint action would be associated with a smaller preferred IPD compared to parallel action. Additionally, given that this research took place in the midst of the COVID-19 pandemic, we aimed to assess whether IPD preferences are affected by individuals’ concerns about infection in general, as well as COVID-19 in particular. We predicted that higher individual concerns would be associated with greater preferred IPD. To test these hypotheses, we asked participants to imagine different social scenarios (involving either joint or parallel actions alongside a stranger) and indicate, on a visual scale, their preferred IPD. The results of two experiments (n = 211, n = 212) showed that participants preferred a shorter distance when they imagined acting jointly compared to when they imagined acting in parallel. Moreover, participants who reported higher discomfort for potential pathogen contact and who were more aware of the COVID-19 context in which the study took place preferred a larger IPD in general. Our results provide further evidence that different types of social interaction shape IPD preference. We discuss potential reasons for this phenomenon and highlight remaining questions for future research.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/8za3r/" target="_blank">Smaller preferred interpersonal distance for joint versus parallel action</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>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Glucocorticoid<br/><b>Sponsor</b>: Huashan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of the Effect on Cognitive Skills of COVID-19 Survivors</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: green walking and intelligence gam<br/><b>Sponsors</b>: Bayburt University; Karadeniz Technical University<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>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>: Patients With COVID-19<br/><b>Interventions</b>: Drug: The drug “Rutan 0.1”.; Other: Basic treatment<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>The Effect of Special Discharge Training in the COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: COVID-19 Discharge Education<br/><b>Sponsor</b>: Kilis 7 Aralik University<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>Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19</strong> - <b>Conditions</b>: COVID-19 Vaccine; COVID-19<br/><b>Interventions</b>: Biological: 50 μg Baiya SARS-CoV-2 Vax 2; Other: Placebo<br/><b>Sponsor</b>: Baiya Phytopharm 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>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Arginine Hydrochloride<br/><b>Sponsor</b>: Emory 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>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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>Physiotherapy in Mutated COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Physiotherapy<br/><b>Sponsor</b>: Giresun University<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>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Rutan 25 mg; Other: Control group<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>: Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>: Vielight Inc.<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>To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment.</strong> - <b>Conditions</b>: Fecal Microbiota Transplantation; COVID-19 Infection<br/><b>Intervention</b>: Procedure: Fecal microbiota transplantation<br/><b>Sponsor</b>: Shanghai 10th People’s Hospital<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 a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Other: Spray with Hypochlorous Acid Group; Other: Spray with Placebo Group<br/><b>Sponsor</b>: University of Monastir<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>Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona<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 Vaccine Uptake Amongst Underserved Populations in East London</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccination Refusal<br/><b>Intervention</b>: Device: Patient Engagement tool<br/><b>Sponsors</b>: Queen Mary University of London; Social Action for Health<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>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Baricitinib 4 MG<br/><b>Sponsors</b>: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale University<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir</strong> - CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.</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>Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice</strong> - CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.</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>Promoting cognitive health: a virtual group intervention for community-living older adults</strong> - CONCLUSIONS: The synchronous virtual group intervention was shown to be feasible for the elderly in the community who participated in the study.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19</strong> - The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant…</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>HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway</strong> - Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having 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>Evaluation of the Inhibition Potency of Nirmatrelvir against Main Protease Mutants of SARS-CoV-2 Variants</strong> - SARS-CoV-2 continues to pose a threat to public health. Main protease (M^(pro)) is one of the most lucrative drug targets for developing specific antivirals against SARS-CoV-2 infection. By targeting M^(pro), peptidomimetic nirmatrelvir is able to inhibit viral replication of SARS-CoV-2 and reduce the risk for progression to severe COVID-19. However, multiple mutations in the gene encoding M^(pro) of emerging SARS-CoV-2 variants raise a concern of drug resistance. In the present study, 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>Culture and pandemic control at cross-roads: navigating the burial guidelines for COVID-19-related deaths in a Ghanaian setting</strong> - CONCLUSIONS: Insensitivity to socio-cultural practices compromised the implementation of the COVID-19 pandemic control interventions, particularly, the COVID-19-related death and burial protocols. Some compromises that were not sanctioned by the protocols were reached to allow health officials and families respectfully bury their dead. These findings call for the need to prioritize the incorporation of sociocultural practices in future pandemic prevention and management strategies.</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>Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov)</strong> - Covalent kinase inhibitors (CKIs) hold great promise for drug development. However, examples of computationally guided design of CKIs are still scarce. Here, we present an integrated computational workflow (Kin-Cov) for rational design of CKIs. The design of the first covalent leucine-zipper and sterile-α motif kinase (ZAK) inhibitor was presented as an example to showcase the power of computational workflow for CKI design. The two representative compounds, 7 and 8, inhibited ZAK kinase with…</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>Essential Oil Derived from Underutilized Plants <em>Cymbopogon khasianus</em> Poses Diverse Biological Activities against “<em>Aspergillosis</em>” and “<em>Mucormycosis</em>”</strong> - Palmrosa essential oil (PEO) from Cymbopogon khasianus, is used as complementary and traditional medicine worldwide. The present study aimed at compositional profiling of PEO and molecular docking of PEO bioactive compound geraniol against fungal enzymes chitin synthase (CS), UDP-glycosyltransferase (UDPG) and glucosamine-6-phosphate synthase (GPS), as apposite sites for drug designing against “Aspergillosis” and “Mucormycosis” and in vitro confirmation. Compositional profile of PEO 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>Detection of SARS-CoV-2 Antibodies: Comparison of Enzyme Immunoassay, Surrogate Neutralization and Virus Neutralization Test</strong> - CONCLUSIONS: sVNT appeared to be a reliable method for the assessment COVID-19 serology in patients with high antibody levels, while false-negative results were frequently observed in patients with low NT titers.</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>Elucidating Atomistic Insight into the Dynamical Responses of the SARS-CoV-2 Main Protease for the Binding of Remdesivir Analogues: Leveraging Molecular Mechanics To Decode the Inhibition Mechanism</strong> - To combat mischievous coronavirus disease followed by continuous upgrading of therapeutic strategy against the antibody-resistant variants, the molecular mechanistic understanding of protein-drug interactions is a prerequisite in the context of target-specific rational drug development. Herein, we attempt to decipher the structural basis for the inhibition of SARS-CoV-2 main protease (M^(pro)) through the elemental analysis of potential energy landscape and the associated thermodynamic and…</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>Risk connectedness between crude oil, gold and exchange rates in China: Implications of the COVID-19 pandemic</strong> - This study examined the risk connectedness and its asymmetry between oil, gold, and foreign exchange under the realized volatility, spillover index framework, and high-frequency data during the COVID-19 pandemic. It was found that: (1) At the beginning of the pandemic outbreak, the total volatility spillover in the system declined, which may indicate that the pandemic cuts the trading activities in the financial markets by inhibiting personnel mobility, then, the spillover experienced 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>Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab</strong> - CONCLUSIONS: We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.</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>Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico</strong> - CONCLUSIONS: NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy. PREVENT-19 ClinicalTrials.gov number, NCT04611802.</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>Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices</strong> - The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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