Covid-19 Sentry

Contents

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

From Preprints

• How risky is it to not wear a mask? Moral emotions increase preventative health behaviours during the COVID-19 pandemic in India -
  Given the high transmission rates of the COVID-19 virus, policies aim at the maximal adoption of preventative health behaviours (PHBs) such as mask-wearing and maintaining physical distance. Moral emotions, risk perception, and message frames have previously been shown to foster favourable PHBs during various pandemics. To investigate the factors associated with PHBs during the COVID-19 pandemic, the present study explored the predictive role of moral emotions and message frames on PHBs (reduced physical contact and COVID-19 related policy support), controlling for risk perception regarding wearing a mask. Thus, a 2 (target of the message: self vs others) x 2 (valence: negative vs positive) between-groups experiment was conducted amongst Indians. Negative moral emotions predicted both (reduced) physical contact and policy support, and positive moral emotions predicted policy support. Exposure to differently framed health messages did not predict PHBs. The present study contributes to the field of health communication by highlighting the need for culture-specific practices such as focusing on the affective aspects of such communication. The results are increasingly relevant owing to the continuance of the COVID-19 crisis in India, and suggest that eliciting moral emotions throughCOVID-19 communication may significantly improve compliance with PHBs.
  🖺 Full Text HTML: How risky is it to not wear a mask? Moral emotions increase preventative health behaviours during the COVID-19 pandemic in India
• Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins in Escherichia coli -
  The fundamental biology of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (Ncap), its use in diagnostic assays and its potential application as a vaccine component have received considerable attention since the outbreak of the Covid19 pandemic in late 2019. Here we report the scalable expression and purification of soluble, immunologically active, SARS-CoV-2 Ncap in Escherichia coli. Codon-optimised synthetic genes encoding the original Ncap sequence and four common variants with an N-terminal 6His affinity tag (sequence MHHHHHHG) were cloned into an inducible expression vector carrying a regulated bacteriophage T5 synthetic promoter controlled by lac operator binding sites. The constructs were used to express Ncap proteins and protocols developed which allow efficient production of purified Ncap with yields of over 200 mg per litre of culture media. These proteins were deployed in ELISA assays to allow comparison of their responses to human sera. Our results suggest that there was no detectable difference between the 6His-tagged and untagged original Ncap proteins but there may be a slight loss of sensitivity of sera to other Ncap isolates.
  🖺 Full Text HTML: Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins in Escherichia coli
• Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19 -
  SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.
  🖺 Full Text HTML: Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19
• Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanocrystals Made of Inexpensive Metals - Replacing Gold -
  Different kinds of nanoparticles can be conjugated with diverse biomolecular receptors and employed in biosensing to detect a target analyte (biomarkers of infections, cancer markers, etc.) from biological samples. This proven concept was largely used during the COVID-19 pandemic in over-the-counter gold nanoparticles-based paper strip tests. Considering that gold is expensive and is being largely depleted, here we show that novel and less expensive plasmonic counterparts, titanium nitride (TiN) nanoparticles, and copper nanoparticles covered with a gold shell (Cu@Au) perform comparable or better than gold nanoparticles. After functionalization, these novel nanoparticles provide a high signal, efficiency, and specificity when used on paper strip tests. This allows an easy visual determination of the positive signal and the development of more affordable paper-based test strips. Moreover, by conducting the machine learning study, we have shown that the bio-detection with TiN is more accurate than that with gold, demonstrating the advantage of a broadband plasmonic material. The implementation of lateral flow assays based on TiN and Cu@Au nanoparticles promises a drastic cost reduction of this technology and its widespread applications in tasks of biomedical diagnostics, environmental and food safety, security and doping screening.
  🖺 Full Text HTML: Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanocrystals Made of Inexpensive Metals - Replacing Gold
• PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration -
  As terabytes of multi-omics data are being generated, there is an ever-increasing need for methods facilitating the integration and interpretation of such data. Current multi-omics integration methods typically output lists, clusters, or subnetworks of molecules related to an outcome. Even with expert domain knowledge, discerning the biological processes involved is a time-consuming activity. Here we propose PathIntegrate, a method for integrating multi-omics datasets based on pathways, designed to exploit knowledge of biological systems and thus provide interpretable models for such studies. PathIntegrate employs single-sample pathway analysis to transform multi-omics datasets from the molecular to the pathway-level, and applies a predictive single-view or multi-view model to integrate the data. Model outputs include multi-omics pathways ranked by their contribution to the outcome prediction, the contribution of each omics layer, and the importance of each molecule in a pathway. Using semi-synthetic data we demonstrate the benefit of grouping molecules into pathways to detect signals in low signal-to-noise scenarios, as well as the ability of PathIntegrate to precisely identify important pathways at low effect sizes. Finally, using COPD and COVID-19 data we showcase how PathIntegrate enables convenient integration and interpretation of complex high-dimensional multi-omics datasets. The PathIntegrate Python package is available at https://github.com/cwieder/PathIntegrate.
  🖺 Full Text HTML: PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration
• Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States — September 2022–August 2023 -

  Objective: To evaluate the durability of protection provided by original monovalent and bivalent COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes Design: Multicenter case-control design with prospective enrollment Setting: 26 hospitals in 20 US states Participants: Adults aged ≥18 years admitted to hospital with COVID-19-like illness from 8 September 2022 to 31 August 2023 Main outcome measures: The main outcomes were absolute and relative vaccine effectiveness of original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes, including advanced respiratory support (defined as receipt of high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation [IMV]) and IMV or death. Vaccine effectiveness was estimated using multivariable logistic regression, in which the odds of vaccination (versus being unvaccinated or receiving original monovalent vaccination only) were compared between COVID-19 case patients and control-patients. Bivalent vaccine effectiveness analyses were stratified by time since dose receipt. Results: Among 7028 adults without immunocompromising conditions, 2924 (41.6%) were COVID-19 case patients and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute vaccine effectiveness against COVID-19-associated hospitalization was 6% (-7% to 17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304-571]), 52% (39% to 61%) for a bivalent dose received 7-89 days earlier, and 13% (-10% to 31%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated advanced respiratory support was 31% (15% to 45%) for original monovalent doses only, 66% (47% to 78%) for a bivalent dose received 7-89 days earlier, and 33% (-1% to 55%) for a bivalent dose received 90-179 days earlier. Absolute vaccine effectiveness against COVID-19-associated IMV or death was 51% (34% to 63%) for original monovalent doses only, 61% (35% to 77%) for a bivalent dose received 7-89 days earlier, and 50% (11% to 71%) for a bivalent dose received 90-179 days earlier. Conclusion: When compared to original monovalent vaccination only, bivalent COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only. Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against IMV or death.

  🖺 Full Text HTML: Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States — September 2022–August 2023
• How executive control and emotional reactivity influence coping strategies in psychiatric patients during the COVID-19 pandemic -

  Background: During times of environmental challenges, adaptive coping strategies are essential to maintain mental health. Coping relies on executive control, which is often impaired in individuals with psychiatric disorders. Furthermore, emotional reactivity may interfere with executive control. Studying the association between cognitive skills and adaptive coping strategies, as well as the potential impact of emotional reactivity, could inform how we can provide mental support during large-scale adversity. In this study we examined coping strategies in a thoroughly phenotyped psychiatric cohort, the MIND-Set cohort, during the early COVID-19 pandemic stage. Methods: We studied 1) the association between coping and both subjective and objective executive control before the pandemic, and three different coping strategies used during the pandemic, 2) the mediating role of emotional reactivity, indexed by amygdala reactivity, and 3) the moderating role of the presence of a psychiatric diagnosis in these associations. After finding no specific impact of patient or control status in this association, we decided to post-hoc study the transdiagnostic impact of depression severity in these associations. Results: showed 1) only a significant association between subjective executive control and a self-reported positive reappraisal style and corona-related reappraisal. However, after controlling for depression severity, this association was no longer significant. Additionally, objective executive control was only directly associated with right amygdala reactivity, while amygdala reactivity in neither of the hemispheres mediated the association between executive control and any of the coping styles. Furthermore, the type of diagnosis did not moderate the association between executive control and coping. Conclusion: Our findings firstly underline the difference between self-reported and performance based executive control. While both deficits in subjective and performance based EC may play a role in the persistence of psychiatric symptomatology, this finding emphasizes how depressive symptoms or negative affect can impact reappraisal ability. As this ability is fundamental to staying resilient, treatments focused on reducing negative affect and thereby training reappraisal are pivotal in the maintenance of mental health in the entire population during environmental challenges.

  🖺 Full Text HTML: How executive control and emotional reactivity influence coping strategies in psychiatric patients during the COVID-19 pandemic
• Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants -

  The spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to accumulate substitutions, leading to breakthrough infections of vaccinated individuals and prompting the development of updated booster vaccines. Here, we determined the specificity and functionality of antibody and B cell responses following exposure to BA.5 and XBB variants in individuals who received ancestral SARS-CoV-2 mRNA vaccines. BA.5 exposures elicited antibody responses that primarily targeted epitopes conserved between the BA.5 and ancestral spike, with poor reactivity to the XBB.1.5 variant. XBB exposures also elicited antibody responses that targeted epitopes conserved between the XBB.1.5 and ancestral spike. However, unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals. Pre-existing cross-reactive B cells and antibodies were correlated with stronger overall responses to XBB but weaker XBB-specific responses, suggesting that baseline immunity influences the activation of variant-specific SARS-CoV-2 responses.

  🖺 Full Text HTML: Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants
• Symptoms of children and adolescents infected with SARS-CoV-2 variants alpha, delta or omicron -

  Symptoms experienced by children and adolescents with SARS-CoV-2 infections in the alpha, delta and omicron variant dominated phases were investigated using an online survey, and the frequencies of reported symptoms and changes over time were analyzed. The most prevalent symptoms were fever above 38 degrees Celsius, tiredness, headache, runny or blocked nose, sneezing and dry cough. Lethargy and nausea were reported significantly more frequently in the omicron variant dominated phase than in the earlier phases of the pandemic. Compared to symptoms reported by adults, fever and gastrointestinal symptoms were reported more frequently for children, especially in the omicron variant dominated phase, whereas the frequency of loss of smell and loss of taste was significantly lower in children than in adults.

  🖺 Full Text HTML: Symptoms of children and adolescents infected with SARS-CoV-2 variants alpha, delta or omicron
• Estimation of SARS-CoV-2 fitness gains from genomic surveillance data without prior lineage classification -

  The emergence of SARS-CoV-2 variants with increased fitness has had a strong impact on the epidemiology of COVID-19, with the higher effective reproduction number of the viral variants leading to new epidemic waves. Tracking such variants and their genetic signatures, using data collected through genomic surveillance, is therefore crucial for forecasting likely surges in incidence. Current methods of estimating fitness advantages of variants rely on tracking the changing proportion of a particular lineage over time, but describing successful lineages in a rapidly evolving viral population is a difficult task. We propose a new method of estimating fitness gains directly from nucleotide information generated by genomic surveillance, without a-priori assigning isolates to lineages from phylogenies, based solely on the abundance of Single Nucleotide Polymorphisms (SNPs). The method is based on mapping changes in the genetic population structure over time. Changes in the abundance of SNPs associated with periods of increasing fitness allow for the unbiased discovery of new variants, and thereby obviating a deliberate lineage assignment and phylogenetic inference. We conclude that the method provides a fast and reliable way to estimate fitness advantages of variants without the need for a-priori assigning isolates to lineages.

  🖺 Full Text HTML: Estimation of SARS-CoV-2 fitness gains from genomic surveillance data without prior lineage classification
• Assessing the impact of interventions on the major Omicron BA.2 outbreak in spring 2022 in Shanghai -

  Background Shanghai experienced a significant surge in Omicron BA.2 infections from March to June 2022. In addition to the standard interventions in place at that time, additional interventions were implemented in response to the outbreak. However, the impact of these interventions on BA.2 transmission remains unclear. Methods We systematically collected data on the daily number of newly reported infections during this wave and utilized a Bayesian approach to estimate the daily effective reproduction number. Data on public health responses were retrieved from the Oxford COVID-19 Government Response Tracker and served as a proxy for the interventions implemented during this outbreak. Using a log-linear regression model, we assessed the impact of these interventions on the reproduction number. Furthermore, we developed a mathematical model of BA.2 transmission. By combining the estimated effect of the interventions from the regression model and the transmission model, we estimated the number of infections and deaths averted by the implemented interventions. Results We found a negative association (-0.0069, 95% CI: -0.0096 to -0.0045) between the level of interventions and the number of infections. If interventions did not ramp up during the outbreak, we estimated that the number of infections and deaths would have increased by 22.6% (95% CI: 22.4-22.8%), leading to a total of 768,576 (95% CI: 768,021-769,107) infections and 722 (95% CI: 722-723) deaths. If no interventions were deployed during the outbreak, we estimated that the number of infections and deaths would have increased by 46.0% (95% CI: 45.8-46.2%), leading to a total of 915,099 (95% CI: 914,639-915,518) infections and 860 (95% CI: 860-861) deaths. Conclusion Our findings suggest that the interventions adopted during the Omicron BA.2 outbreak in spring 2022 in Shanghai were effective in reducing SARS-CoV-2 transmission and disease burden. Our findings emphasize the importance of non-pharmacological interventions in controlling quick surges of cases during epidemic outbreaks.

  🖺 Full Text HTML: Assessing the impact of interventions on the major Omicron BA.2 outbreak in spring 2022 in Shanghai
• homeRNA self-blood collection enables high-frequency temporal profiling of the pre-symptomatic host immune kinetics to respiratory viral infection: a prospective cohort study -

  Background Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual′s infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a self-blood collection tool (homeRNA) to profile detailed kinetics of the pre-symptomatic to convalescence host immunity to contemporaneous respiratory pathogens. Methods We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self–collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS–CoV–2 and common respiratory pathogens. 92 longitudinal blood samples spanning the pre–shedding to post–acute phase of eight SARS–CoV–2–infected participants and 40 interval–matched samples from four exposed–uninfected participants were subjected to high–frequency longitudinal profiling of 773 host immune genes. Findings Between June 2021 – April 2022, 68 participants across 26 U.S. states completed the study and self–collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS–CoV–2 was detected in 17 out of 22 individuals with study–confirmed respiratory infection. With rapid dissemination of home self–collection kits, two and four COVID-19+ participants started collection prior to viral shedding and symptom onset, respectively, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. In pre–shedding samples, we observed transient but robust expression of T–cell response signatures, transcription factor complexes, prostaglandin biosynthesis genes, pyrogenic cytokines, and cytotoxic granule genes. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load. Finally, we observed increased expression of host defense peptides (HDPs) in exposed-uninfected individuals over the 4–week observational window. Interpretation We demonstrated that unsupervised self–collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large–scale population–wide longitudinal mechanistic studies. Expression of cytotoxic/T–cell signatures in pre–shedding samples preceding expansion of innate ISGs suggests a potential role for T–cell mediated pathogen control during early infection. Elevated expression of HDPs in exposed–uninfected individuals warrants further validation studies to assess their potential role in protective immunity during pathogen exposure.

  🖺 Full Text HTML: homeRNA self-blood collection enables high-frequency temporal profiling of the pre-symptomatic host immune kinetics to respiratory viral infection: a prospective cohort study
• Associations of proton pump inhibitors with susceptibility to pneumonia, influenza, and COVID-19: evidence from a large population based cohort study -

  Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95%CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not associated with regular PPI use (HR 1.08, 95%CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95%CI 1.11-1.27) and mortality (HR 1.37. 95%CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95%CI 1.19-2.54), but not pneumonia or COVID-19-related outcomes. In conclusion, PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required.

  🖺 Full Text HTML: Associations of proton pump inhibitors with susceptibility to pneumonia, influenza, and COVID-19: evidence from a large population based cohort study
• Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens -
  Considerable loss of life, economic slowdown, and public health risk associated with the transmission of airborne respiratory pathogens was underscored by the recent COVID-19 pandemic. Airborne transmission of zoonotic diseases such as the highly pathogenic avian influenza (HPAI) and porcine reproductive and respiratory syndrome virus (PRRSV) has caused major disruptions to domestic and global food security. Current ambient air pathogen monitoring systems involves the collection of air samples from indoor settings suspected of viral contamination, followed by subsequent processing of capture samples to determine the presence and species of airborne viral matter. Nucleic acid amplification techniques are considered the gold standard for pathogen diagnostics. Currently, the necessary extraction and purification of viral RNA from air collector systems prior to sample analysis is both time consuming and performed manually. A monitoring system with separate air sampling and biochemical detection procedures is prone to delay the response to emergent viral threats. In this paper, we present a pathogen monitoring system that overcomes these limitations related to extraction and purification of viral samples and lays the groundwork for a real-time monitor for airborne viral pathogens. We demonstrate a high flow electrostatic precipitator system, that uses small collection wells as counter electrodes for pathogen collection. Integrated reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) is used for detection of captured viral matter within wells. On-chip heating of collection wells is enabled by integrated planar heaters and small volumes of reagent (30 ) directly to the collection wells. We present the design of such a system and show experimental results that demonstrate the use of this device for detection of aerosolized SARS- CoV-2 virus like particles (VLPs), a model pathogen for SARV-CoV-2.
  🖺 Full Text HTML: Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens
• Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19 -
  Background: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19. Methods: Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection. Results: COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca2+ handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant. Conclusions: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.
  🖺 Full Text HTML: Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19

From Clinical Trials

• Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19 - Conditions: Mild to Moderate COVID-19
  Interventions: Drug: WPV01; Drug: Placebo
  Sponsors: Westlake Pharmaceuticals (Hangzhou) Co., Ltd.
  Recruiting

• Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers - Conditions: COVID-19 Infection
  Interventions: Other: Mindfulness-based Health Qigong Intervention
  Sponsors: The Hong Kong Polytechnic University
  Recruiting

• SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings - Conditions: SARS-CoV-2 Infection; Influenza A; Influenza B
  Interventions: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test
  Sponsors: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority
  Recruiting

• Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial - Conditions: COVID-19
  Interventions: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement
  Sponsors: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services
  Not yet recruiting

• Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients - Conditions: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome
  Interventions: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy
  Sponsors: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University
  Active, not recruiting

• Long COVID Ultrasound Trial - Conditions: Long Covid
  Interventions: Device: Splenic Ultrasound
  Sponsors: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense)
  Recruiting

• Immunogenicity After COVID-19 Vaccines in Adapted Schedules - Conditions: Coronavirus Disease 2019; COVID-19
  Interventions: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant]
  Sponsors: Universiteit Antwerpen
  Completed

• Could Wearing Face Mask Have Affected Demodex Parasite - Conditions: Pandemic, COVID-19; Demodex Infestation
  Interventions: Diagnostic Test: standard superficial skin biopsy (SSSB)
  Sponsors: Nurhan Döner Aktaş
  Completed

• TDCS Stimulation After Covid-19 Infection - Conditions: COVID-19
  Interventions: Procedure: Transcranial Direct Stimulation
  Sponsors: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat University
  Recruiting

From PubMed

• Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design - Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for preventing future COVID outbreaks. The SARS-CoV-2 main protease (M^(pro)), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that M^(pro) is subject to redox regulation in vitro and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues….

• Antibacterial and Antiviral Activities of Silver Nanocluster/Silica Composite Coatings Deposited onto Air Filters - The indoor air quality should be better controlled and improved to avoid numerous health issues. Even if different devices are developed for air filtration, the proliferation of microorganisms under certain conditions must be controlled. For this purpose, a silver nanocluster/silica composite coating was deposited via a cosputtering technique onto fiber glass and polymeric based substrates. The aim of this work is focused on the evaluation of the antibacterial and antiviral effects of the…

• Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2⁺ Cells - The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2^(+) lung cells during a viral infection cycle should prevent viral S protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, we construct dual-drug-combined…

• In silico Evaluation of ACE2 Inhibition by Prunus armeniaca L. and in vivo Toxicity Study - CONCLUSION: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.

• Design, Synthesis, X-ray Crystallography, and Biological Activities of Covalent, Non-Peptidic Inhibitors of SARS-CoV-2 Main Protease - Highly contagious SARS-CoV-2 coronavirus has infected billions of people worldwide with flu-like symptoms since its emergence in 2019. It has caused deaths of several million people. The viral main protease (Mpro) is essential for SARS-CoV-2 replication and therefore a drug target. Several series of covalent inhibitors of Mpro were designed and synthesized. Structure-activity relationship studies show that (1) several chloroacetamide- and epoxide-based compounds targeting Cys145 are potent…

• Anti-SARS-CoV-2 Activity of a Polyphenolic Complex from Maackia amurensis - We studied the ability of the polyphenolic complex from Maackia amurensis, the active substance of Maksar, to inhibit the cytopathogenic effect induced by the SARS-CoV-2 and to reduce the concentration of viral RNA in infected Vero E6 cells. Polyphenolic complex showed significant anti-SARS-CoV-2 activity and effectively inhibited viral replication by direct action on viral particles and the early stage of viral infection.

• Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies - Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the…

• Two Receptor Binding Strategy of SARS-CoV-2 Is Mediated by Both the N-Terminal and Receptor-Binding Spike Domain - It is not well understood why severe acute respiratory syndrome (SARS)-CoV-2 spreads much faster than other β-coronaviruses such as SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. In a previous publication, we predicted the binding of the N-terminal domain (NTD) of SARS-CoV-2 spike to sialic acids (SAs). Here, we experimentally validate this interaction and present simulations that reveal a second possible interaction between SAs and the spike protein via a binding site located in the…

• Cyclooxygenase-2/prostaglandin E2 pathway regulates infectious bronchitis virus replication in avian macrophages - Infectious bronchitis virus (IBV) is a significant respiratory pathogen that affects chickens worldwide. As an avian coronavirus, IBV leads to productive infection in chicken macrophages. However, the effects of IBV infection in macrophages on cyclooxygenase-2 (COX-2) expression are still to be elucidated. Therefore, we investigated the role of IBV infection on the production of COX-2, an enzyme involved in the synthesis of prostaglandin E2 (PGE2) in chicken macrophages. The chicken macrophage…

• Evaluation of natural products from virtual screenings as SARS-CoV-2 main protease inhibitors using combinational experiments - Recently, andrographolide, kaempferol, maslinic acid, rutin, and schaftoside have been identified as potent SARS-CoV-2 main protease (Mpro) inhibitors via molecular docking studies. However, no comprehensive in vitro testing of these compounds against Mpro has been conducted. In this study, we rigorously evaluated the in vitro inhibition of Mpro by these compounds using combinational experiments, including fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and…

• Chemical and spectroscopic characterization of (Artemisinin/Querctin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats - A novel Artemisinin/Quercetin/Zinc (Art/Q/Zn) mixed ligand complex was synthesized, tested for its antiviral activity against coronavirus (SARS-CoV-2), and investigated for its effect against toxicity and oxidative stress induced by acrylamide (Acy), which develops upon cooking starchy foods at high temperatures. The synthesized complex was chemically characterized by performing elemental analysis, conductance measurements, FT-IR, UV, magnetic measurements, and XRD. The morphological surface of…

• High production MBL2 polymorphisms protect against COVID-19 complications in critically ill patients: A retrospective cohort study - Mannose-binding lectin (MBL) binds to SARS-CoV-2, inhibits infection of susceptible cells, and activates the complement system via the lectin pathway. In this study, we investigated the association of MBL2 polymorphisms with the risk of hospitalization and clinical worsening in patients with COVID-19. A total of 550 patients with COVID-19 were included (94 non-hospitalized and 456 hospitalized). Polymorphisms in MBL2 exon 1 (codons 52, 54 and 57) and promoter region (-550, -221, and +4) were…

• Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein - SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing…

• Development of an integrated sample amplification control for salivary point-of-care pathogen testing - BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive…

• Multifunctional polymeric guanidine and hydantoin halamines with broad biocidal activity - Prolonged and excessive use of biocides during the coronavirus disease era calls for incorporating new antiviral polymers that enhance the surface design and functionality for existing and potential future pandemics. Herein, we investigated previously unexplored polyamines with nucleophilic biguanide, guanidine, and hydantoin groups that all can be halogenated leading to high contents of oxidizing halogen that enables enhancement of the biocidal activity. Primary amino groups can be used to…

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