Covid-19 Sentry

Contents

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

From Preprints

• Impact of State Telehealth Parity Laws for Private Payers on Hypertension Management before and during the COVID-19 Pandemic -

  BACKGROUND: Telehealth has emerged as an effective tool for managing common chronic conditions such as hypertension, especially during the COVID-19 pandemic. However, the impact of state telehealth payment and coverage parity laws on hypertension management remains uncertain. METHODS: Data from the MerativeTM MarketScan® Commercial Claims and Encounters Database from January 1, 2016 to December 31, 2021 were used to construct the study cohort. The sample included non-pregnant individuals aged 25?64 years with hypertension. We reviewed and coded telehealth parity laws related to hypertension management in all 50 states and the District of Columbia, distinguishing between payment parity laws and coverage parity laws. The primary outcomes were antihypertension medication use, measured by the average medication possession ratio (MPR), medication adherence (MPR ?80%), and average number of days of drug supply. We used a generalized difference-in-difference (DID) design to examine the impact of these laws. Results were presented as marginal effects and 95% confidence intervals (CI). RESULTS: Among 353,220 individuals, states with payment parity laws were significantly linked to increased average MPR by 0.43 percentage point (95% CI: 0.07 - 0.79), and an increase of 0.46 percentage point (95% CI: 0.06 - 0.92) in the probability of medication adherence. Payment parity laws also led to an average increase of 2.14 days (95% CI: 0.11 - 4.17) in antihypertensive drug supply, after controlling for state-fixed effects, year-fixed effects, individual sociodemographic characteristics and state time-varying covariates including unemployment rates, GDP per capita, and poverty rates. In contrast, coverage parity laws were associated with a 2.13-day increase (95% CI: 0.19 - 4.07) in days of drug supply, but did not significantly increase the average MPR or probability of medication adherence. In addition, telehealth payment or coverage parity laws were positively associated with the number of hypertension-related telehealth visits, but this effect did not reach statistical significance. These findings were consistent in sensitivity analyses. CONCLUSIONS: State telehealth payment parity laws were significantly associated with greater medication adherence, whereas coverage parity laws were not. With the increasing adoption of telehealth parity laws across states, these findings may support policymakers in understanding potential implications on management of hypertension.

  🖺 Full Text HTML: Impact of State Telehealth Parity Laws for Private Payers on Hypertension Management before and during the COVID-19 Pandemic
• Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients - March 2022 - April 2023. -

  Objective: Develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for clinical and research applications. Material and Methods: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors , including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to model risks. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. Results: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. Discussion: These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. Conclusions: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments.

  🖺 Full Text HTML: Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients - March 2022 - April 2023.
• Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021 to June 2022 -

  To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.

  🖺 Full Text HTML: Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021 to June 2022
• Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub -

  Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023–April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023–April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023–April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November–January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000–4,270,000) hospitalizations and 209,000 (90% PI: 139,000–461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000–355,000) fewer hospitalizations and 33,000 (95% CI: 12,000–54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI: 29,000–69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.

  🖺 Full Text HTML: Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub
• Fluoxetine promotes immunometabolic defenses to mediate host-pathogen cooperation during sepsis -
  Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world. While they are used for their ability to increase serotonergic signaling in the brain, SSRIs are also known to have a broad range of effects beyond the brain, including immune and metabolic effects. Recent studies have demonstrated that SSRIs are protective in animal models and humans against several infections, including sepsis and COVID-19, however the mechanisms underlying this protection are largely unknown. Here we mechanistically link two previously described effects of the SSRI fluoxetine in mediating protection against sepsis. We show that fluoxetine-mediated protection is independent of peripheral serotonin, and instead increases levels of circulating IL-10. IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia and cardiac triglyceride accumulation, allowing for metabolic reprogramming of the heart. Our work reveals a beneficial off-target effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.
  🖺 Full Text HTML: Fluoxetine promotes immunometabolic defenses to mediate host-pathogen cooperation during sepsis
• Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response -
  Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in the Malawi cohort, by response to interferon-gamma in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.
  🖺 Full Text HTML: Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response
• Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling. -
  Assessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holo-tomographic microscopy (HTM) with Artificial Intelligence (AI) to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets (LD) and mitochondria within hundreds of single cells from early infection to syncytia formation and death. SARS-CoV-2 infection enlarges nucleoli, perturbs LD, changes mitochondrial shape and dry mass, and separates LD from mitochondria. We then used Bayesian statistics on organelle dry mass states to define organelle cross-regulation (OCR) networks and report modifications of OCR that are triggered by infection and syncytia formation. Our work highlights the subcellular remodeling induced by SARS-CoV-2 infection and provides a new AI-enhanced, label-free methodology to study in real-time the dynamics of cell populations and their content.
  🖺 Full Text HTML: Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling.
• Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers -
  Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFN{gamma} ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 reliably immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.
  🖺 Full Text HTML: Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers
• Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations -
  SARS-CoV-2 mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape, are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we show that the human microbiota may contribute to mutations in variants of concern (VOCs). We identified a mutation and adjacent 6 amino acids (aa) in a viral mutation fragment (VMF) and searched for homologous fragments (HFs) in the National Center for Biotechnology Information (NCBI) database. Among the approximate 8000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is a 12-fold higher than the natural variable proportion. Approximately 70% of these bacterial species belong to the human microbiota, are primarily distributed in the gut or lung and exhibit a composition pattern similar to that of COVID-19 patients. Importantly, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. Collectively, SARS-CoV-2 may acquire mutations from the human microbiota, resulting in alterations in the binding sites or antigenic determinants of the original virus. Our study sheds light on the evolving mutational mechanisms of SARS-CoV-2.
  🖺 Full Text HTML: Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations
• Krisp: A python package for designing CRISPR and amplification-based diagnostic assays from whole genome data -
  Recent pandemics such as COVID-19 have highlighted the importance of rapidly developing diagnostics to detect and monitor evolving pathogens. CRISPR-Cas technology, combined with isothermal DNA amplification methods, has recently been used to develop diagnostic assays for sequence-specific recognition of DNA or RNA. These assays have similar sensitivity to the gold standard qPCR but can be deployed as easy to use and inexpensive test strips. However, the discovery of diagnostic regions of a genome flanked by conserved regions where primers can be designed requires extensive bioinformatic analyses of genome sequences. We developed the python package krisp to find primers and diagnostic sequences that differentiate groups of samples from each other at any taxonomic scale, using either unaligned genome sequences or a variant call format (VCF) file as input. Krisp has been optimized to handle large datasets by using efficient algorithms that run in near linear time, use minimal RAM, and leverage parallel processing when available. The validity of krisp results has been demonstrated in the laboratory with the successful design of SHERLOCK assays to distinguish the sudden oak death pathogen Phytophthora ramorum from closely related Phytophthora species. Krisp is released open source under a permissive license with all the documentation needed to quickly design CRISPR-Cas diagnostic assays.
  🖺 Full Text HTML: Krisp: A python package for designing CRISPR and amplification-based diagnostic assays from whole genome data
• Unveiling the Emotional Turmoil: How Covid-19 impacted researchers and the pursuit of emotional well-being in academia. -
  The Covid-19 crisis unprecedentedly required researchers to adapt to significant changes in their work and personal lives. Our study aims to fill this gap analysing the Covid-19 emotional impact and confinement potential disruptions on researchers activity (specifically, those related to working conditions, caring responsibilities, health, balance, and social support) considering the modulating role played by age, gender, and job position. An online survey was distributed during the first lockdown period of the Covid-19 pandemic, and answers from 1301 researchers (ECR %, senior researchers %) working in Sciences (28.1%), Social Sciences (25.9%), Humanities (16.2%), Health (16.2%) and in Engineering and Architecture (13.5%) were collected. The study highlights that the initial lockdown during the Covid-19 pandemic had a significant emotional impact on researchers, exacerbating pre-existing emotional distress and burnout within this group. Factors such as age, health, gender, and difficulties in balancing work and family life were associated with an increased risk of burnout and emotional distress. Lack of social support was identified as a significant risk factor, while the academic culture prioritizing productivity over well-being contributed to the issue. These findings underscore the need for greater support and cultural changes in academia to preserve researchers' mental health and prevent the chronicization of mental health issues in young academics.
  🖺 Full Text HTML: Unveiling the Emotional Turmoil: How Covid-19 impacted researchers and the pursuit of emotional well-being in academia.
• Extending the welcome: a pluralist and coevolutionary analysis of the transformation of induction and transition provision -
  This paper reflects on an institution-wide transformation of student welcome, induction and transition (WIT) at a large, research-intensive UK university, a change accelerated by the Covid-19 pandemic. The paper examines this process of change, from its origins, through its evolution, and co-evolution, over three academic years since the onset of the Pandemic. To do so, the paper adopts a pluralist approach, utilising theories of change established in higher education literature: Kift’s transition pedagogy and Kotter’s model of organisational change. Crucially, it augments these with a co-evolutionary approach examining interacting populations, learning and qualitative change, which may provide useful insights to other institutions navigating changes to WIT provision.
  🖺 Full Text HTML: Extending the welcome: a pluralist and coevolutionary analysis of the transformation of induction and transition provision
• Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown -
  Covid-19 lockdowns provided ecologists with a rare opportunity to examine how animals behave when humans are absent. Indeed many studies reported various effects of lockdowns on animal activity, especially in urban areas and other human-dominated habitats. We explored how Covid-19 lockdowns in Israel have influenced bird activity in an urban environment by using continuous acoustic recordings to monitor three common bird species that differ in their level of adaptation to the urban ecosystem: (1) the hooded crow, an urban exploiter, which depends heavily on anthropogenic resources; (2) the rose-ringed parakeet, an invasive alien species that has adapted to exploit human resources; and (3) the graceful prinia, an urban adapter, which is relatively shy of humans and can be found urban habitats with shrubs and prairies. Acoustic recordings provided continuous monitoring of bird activity without an effect of the observer on the animal. We performed dense sampling of a 1.3 square km area in northern Tel-Aviv by placing 17 recorders for more than a month in different micro-habitats within this region including roads, residential areas and urban parks. We monitored both lockdown and no-lockdown periods. We portray a complex dynamic system where the activity of specific bird species depended on many environmental parameters and decreases or increases in a habitat-dependent manner during lockdown. Specifically, urban exploiter species decreased their activity in most urban habitats during lockdown, while human adapter species increased their activity during lockdown especially in parks where humans were absent. Our results also demonstrate the value of different habitats within urban environments for animal activity, specifically highlighting the importance of urban parks. These species- and habitat-specific changes in activity might explain the contradicting results reported by others who have not performed a habitat specific analysis.
  🖺 Full Text HTML: Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown
• Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting virus-specific enzymes -
  The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules targeting the SARS-CoV-2 virus-specific proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50) values ranging from 1.42 to 32.7 M. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin exhibit potent anti-SARS-CoV-2 activity in cell-based assays, with half-maximum effective concentration (EC50) values of 21.73 M and 31.19 M, respectively. The anti-inflammatory role of azadirachtin and withanolide_A when assessed using HEK293T cells were found to significantly reduce the levels of CXCL10, TNF, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2 specific enzymes and also host immune pathways involved in virus mediated inflammation.
  🖺 Full Text HTML: Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting virus-specific enzymes
• DEFEN-CE: Social Dialogue in Defence of Vulnerable Groupsin Post?COVID-19 Labour Markets. Report on Czechia and Slovakia -
  This report is part of the EC-funded research project DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets (VS/2021/0196). It scrutinizes how social partners influenced COVID-19-related policy responses towards vulnerable groups in the labour market, and whether this experience created opportunities for strengthening social dialogue in general. The empirical focus is on Czechia and Slovakia as representatives of embedded neoliberal countries. This means liberalizing labour market policies during their economic transition starting in the 1990s, but at the same time, anchoring some institutional mechanisms of policy-making, including social dialogue at the national level. The analysis is based on new empirical data in two dimensions: • primary data on policy measures relevant for the vulnerable groups in the labour market, categorized in a standard database of the most important COVID-19 measures relevant for vulnerable groups. • 19 original semi-structured interviews with employer organizations, trade unions, governments, and NGOs in Czechia and Slovakia, implemented in 2022-2023.
  🖺 Full Text HTML: DEFEN-CE: Social Dialogue in Defence of Vulnerable Groupsin Post?COVID-19 Labour Markets. Report on Czechia and Slovakia

From Clinical Trials

• Cognitive Rehabilitation in Post-COVID-19 Syndrome - Conditions: Post-COVID-19 Syndrome
  Interventions: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group
  Sponsors: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19 - Conditions: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine
  Interventions: Device: Training with a Robotic Hand Exoskeleton
  Sponsors: University of Valladolid; Centro Hospitalario Padre Benito Menni
  Completed

• Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age - Conditions: SARS-CoV-2 Infection; COVID-19
  Interventions: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine
  Sponsors: Pfizer
  Completed

• A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial - Conditions: Long COVID-19 Syndrome; Chronic Fatigue Syndrome
  Interventions: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet
  Sponsors: Cardresearch
  Recruiting

• Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel - Conditions: COVID-19; Influenza A; Influenza B
  Interventions: Diagnostic Test: Panbio™
  Sponsors: Abbott Rapid Dx
  Recruiting

• Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities - Conditions: COVID-19; Vaccine
  Interventions: Behavioral: REDES; Behavioral: Control
  Sponsors: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University
  Recruiting

• The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray - Conditions: SARS-CoV-2; Prevention
  Interventions: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient
  Sponsors: The Second Affiliated Hospital of Chongqing Medical University
  Recruiting

• Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes - Conditions: Normobaric Hypoxia; Hypoventilation; Normoxia
  Interventions: Other: Repeated sprint
  Sponsors: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use - Conditions: COVID-19; Influenza A; Influenza Type B
  Interventions: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel
  Sponsors: Abbott Rapid Dx
  Recruiting

• Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening - Conditions: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance
  Interventions: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot
  Sponsors: Tulane University; National Heart, Lung, and Blood Institute (NHLBI)
  Recruiting

• Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19 - Conditions: Post-COVID-19 Syndrome
  Interventions: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation without maintenance program
  Sponsors: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design)
  Not yet recruiting

• Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention - Conditions: Child Mental Health
  Interventions: Behavioral: Child Mental Health Literacy Program
  Sponsors: Universidad de Valparaiso
  Recruiting

• Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression - Conditions: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19
  Interventions: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging
  Sponsors: City University of New York, School of Public Health; University of North Carolina, Chapel Hill
  Not yet recruiting

From PubMed

• Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract - Inflammatory airway diseases like cystic fibrosis, asthma and COVID-19 are characterized by high levels of pulmonary cytokines. Two well-established antiparasitic drugs, niclosamide and ivermectin, are intensively discussed for the treatment of viral inflammatory airway infections. Here, we examined these repurposed drugs with respect to their anti-inflammatory effects in airways in vivo and in vitro. Niclosamide reduced mucus content, eosinophilic infiltration and cell death in asthmatic mouse…

• Identification of synthetically tractable MERS-CoV main protease inhibitors using structure-based virtual screening and molecular dynamics potential of mean force (PMF) calculations - The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially lethal infection that presents a substantial threat to health, especially in Middle East nations. Given that no FDA-approved specific therapy for MERS infection exists, designing and discovering a potent antiviral therapy for MERS-CoV is crucial. One pivotal strategy for inhibiting MERS replication is to focus on the viral main protease (M^(pro)). In this study, we identify potential novel M^(pro) inhibitors employing…

• CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation - The G protein-coupled receptor ADGRE5 (CD97) binds to various metabolites that play crucial regulatory roles in metabolism. However, its function in the antiviral innate immune response remains to be determined. In this study, we report that CD97 inhibits virus-induced type-I interferon (IFN-I) release and enhances RNA virus replication in cells and mice. CD97 was identified as a new negative regulator of the innate immune receptor RIG-I, and RIG-1 degradation led to the suppression of the IFN-I…

• Inhibition of SARS-CoV-2 3CL protease by the anti-viral chimeric protein RetroMAD1 - COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CL^(pro) and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The…

• Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery - As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued…

• Compounds derived from Humulus lupulus inhibit SARS-CoV-2 papain-like protease and virus replication - CONCLUSION: In addition to the already known inhibition of M^(pro) by XN, our results show, for the first time, that hop-derived compounds target also SARS-CoV-2 PL^(pro) which is a promising therapeutic target as it contributes to both viral replication and modulation of the immune system. These findings support the possibility to develop new hop-derived antiviral drugs targeting human coronaviruses.

• Type I interferon signaling induces a delayed antiproliferative response in respiratory epithelial cells during SARS-CoV-2 infection - The proliferation of respiratory epithelial cells is crucial to host recovery from acute lung injury caused by SARS-CoV-2 and other viral pathogens, but the molecular pathways that govern this process are poorly understood. We performed a high-throughput CRISPR screen that surprisingly revealed a detrimental effect of specific host response, type I interferon (IFN-I) signaling, on the fitness of SARS-CoV-2-infected Calu-3 cells. While IFN-I signaling has been previously associated with several…

• Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses - The emerging viruses SARS-CoV-2 and arenaviruses cause severe respiratory and hemorrhagic diseases, respectively. The production of infectious particles of both viruses and virus spread in tissues requires cleavage of surface glycoproteins (GPs) by host proprotein convertases (PCs). SARS-CoV-2 and arenaviruses rely on GP cleavage by PCs furin and subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), respectively. We report improved luciferase-based reporter cell lines, named luminescent…

• Identification of Ebselen derivatives as novel SARS-CoV-2 main protease inhibitors: Design, synthesis, biological evaluation, and structure-activity relationships exploration - The main protease (M^(pro)) represents one of the most effective and attractive targets for designing anti-SARS-CoV-2 drugs. In this study, we designed and synthesized a novel series of Ebselen derivatives by incorporating privileged fragments from different pockets of the M^(pro) active site. Among these compounds, 11 compounds showed submicromolar activity in the FRET-based SARS-CoV-2 M^(pro) inhibition assay, with IC(50) values ranging from 233 nM to 550 nM. Notably, compound 3a displayed…

• Traditional Formulations for Managing COVID-19: A Systematic Review - Background: The advancing etiopathogenesis, diagnosis, and treatment of the global coronavirus disease 2019 (COVID-19) pandemic have prompted the medical community to consider Ayurveda, Siddha, and Unani as add-on preventive and therapeutic options. Objective: To explore the effect of standalone or integrative Traditional Formulations (TFs) on selected clinical symptoms and biomarkers of COVID-19. Search strategy: Out of 465 articles identified from PubMed, ScienceDirect, and Scopus, 17…

• Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases - Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were…

• Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV-2 Infection - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in high morbidity and mortality rates worldwide. Although the epidemic has been controlled in many areas and numerous patients have been successfully treated, the risk of reinfection persists due to the low neutralizing antibody titers and weak immune response. To provide long-term immune protection for infected patients, novel bispecific CB6/dendritic cell (DC)-specific…

• Molecular Design of Novel Inhibitor by TargetingIL-6Rα using Combined Pharmacophore and Experimentally Verified Plant Products with Scaffold-Hopping Techniques: A Dual Therapeutic Strategy for COVID-19 and Cancer - The IL-6/IL-6R/gp130 complex serves as a significant indicator of cytokine release syndrome in COVID-19 and chronic inflammation, increasing the risk of cancer. Therefore, we identified IL-6Rα as a potential target to block gp130 interaction. Notably, there has been no reception of approval for an orally available drug to serve this purpose, to date. In this study, we targeted IL-6Rα to inhibit IL-6Rα/gp130 interaction. The selection of the lead candidate L821 involved the amalgamation of three…

• The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity - Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection….

• Structure-based virtual screening, ADMET analysis, and molecular dynamics simulation of Moroccan natural compounds as candidates for the SARS-CoV-2 inhibitors - The lack of treatments and vaccines effective against SARS-CoV-2 has forced us to explore natural compounds that could potentially inhibit this virus. Additionally, Morocco is renowned for its rich plant diversity and traditional medicinal uses, which inspires us to leverage our cultural heritage and the abundance of natural resources in our country for therapeutic purposes. In this study, an extensive investigation was conducted to gather a collection of phytoconstituents extracted from…

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