Covid-19 Sentry

Contents

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

From Preprints

• Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung -
  Early stages of deadly respiratory diseases such as COVID-19 have been challenging to elucidate due to lack of an experimental system that recapitulates the cellular and structural complexity of the human lung while allowing precise control over disease initiation and systematic interrogation of molecular events at cellular resolution. Here we show healthy human lung slices cultured ex vivo can be productively infected with SARS-CoV-2, and the cellular tropism of the virus and its distinct and dynamic effects on host cell gene expression can be determined by single cell RNA sequencing and reconstruction of “infection pseudotime” for individual lung cell types. This revealed that the prominent SARS-CoV-2 target is a population of activated interstitial macrophages (IMs), which as infection proceeds accumulate thousands of viral RNA molecules per cell, comprising up to 60% of the cellular transcriptome and including canonical and novel subgenomic RNAs. During viral takeover of IMs, there is cell-autonomous induction of a pro-fibrotic program (TGFB1, SPP1), and an inflammatory program characterized by the early interferon response, chemokines (CCL2, 7, 8, 13, CXCL10) and cytokines (IL6, IL10), along with destruction of cellular architecture and formation of dense viral genomic RNA bodies revealed by super-resolution microscopy. In contrast, alveolar macrophages (AMs) showed neither viral takeover nor induction of a substantial inflammatory response, although both purified AMs and IMs supported production of infectious virions. Spike-dependent viral entry into AMs was neutralized by blockade of ACE2 or Sialoadhesin/CD169, whereas IM entry was neutralized only by DC-SIGN/CD209 blockade. These results provide a molecular characterization of the initiation of COVID-19 in human lung tissue, identify activated IMs as a prominent site of viral takeover and focus of inflammation and fibrosis, and suggest therapeutic targeting of the DC-SIGN/CD209 entry mechanism to prevent IM infection, destruction and early pathology in COVID-19 pneumonia. Our approach can be generalized to define the initiation program and evaluate therapeutics for any human lung infection at cellular resolution.
  🖺 Full Text HTML: Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung
• Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases -

  Background: Societal separation of unvaccinated people from public spaces has been a novel and controversial COVID-era public health practice in many countries. Models exploring potential consequences of vaccination-status-based separation have not considered how separation influences the contact frequencies in the separated groups; we systematically investigate implementing effects of separation on population-specific contact frequencies and show this critically determines the predicted epidemiological outcomes, focusing on the attack rates in the vaccinated and unvaccinated populations and the share of infections among vaccinated people that were due to contacts with infectious unvaccinated people. Methods: We describe a susceptible-infectious-recovered (SIR) two-population model for vaccinated and unvaccinated groups of individuals that transmit an infectious disease by person-to-person contact. The degree of separation between the two groups, ranging from zero to complete separation, is implemented using the like-to-like mixing approach developed for sexually-transmitted diseases [1-3], adapted for presumed SARS-CoV-2 transmission. We allow the contact frequencies for individuals in the two groups to be different and depend, with variable strength, on the degree of separation. Results: Separation can either increase or decrease the attack rate among the vaccinated, depending on the type of separation (isolating or compounding), and the contagiousness of the disease. For diseases with low contagiousness, separation can cause an attack rate in the vaccinated, which does not occur without separation. Interpretation: There is no blanket epidemiological advantage to separation, either for the vaccinated or the unvaccinated. Negative epidemiological consequences can occur for both groups.

  🖺 Full Text HTML: Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases
• Power users: Technology and Canadian sex workers during COVID-19 -
  The transition from physical to online advertising by sex workers in Canada has been well documented. However, few studies use rigorous sampling methods. This study considers how a technically sophisticated group of advertisers from a large Canadian sex work classifieds site used multiple online resources to promote or provide services during the COVID-19 pandemic. Advertisers qualified for the study if they used a URL as part of their contact information and were actively advertising between August 23 and September 22, 2022. A random sample of 1000 qualifying advertisers were selected of which 783 had accessible contact URLs. Themes were identified in downloaded website texts using grounded theory analysis. Ad metadata was used to identify demographic and behavioral distinctions between the sample and other advertisers. Almost all sampled advertisers (99%) provided in person services and most (70%) provided online services. The sample advertised more frequently, were more affluent and were more likely to be Anglophone, White, trans-female, or provide BDSM services. Themes of security, health, identity, and social networks were identified. Advertisers emphasized physical, emotional, and financial security. Most workers did not work in isolation and many participated in extensive social networks.
  🖺 Full Text HTML: Power users: Technology and Canadian sex workers during COVID-19
• Epigenetic Age Acceleration in Surviving versus Deceased COVID-19 Patients with Acute Respiratory Distress Syndrome following Hospitalization -
  Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in a variety of tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS) has not been well investigated. In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiples time-points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion vs end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased vs recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID19 patients between inclusion and end of follow-up as well as a significant change in dynamic telomere attrition acceleration when comparing patients who recovered vs those who died. In conclusion, EAA and telomere attrition acceleration was associated with treatment outcome in hospitalized COVID-19 Patients with ARDS. A better understanding of the long-term effects of EAA in COVID19 patients and how they might contribute to Long COVID symptoms in recovered individuals is urgently needed.
  🖺 Full Text HTML: Epigenetic Age Acceleration in Surviving versus Deceased COVID-19 Patients with Acute Respiratory Distress Syndrome following Hospitalization
• Deep mutational scanning of whole SARS-CoV-2 spike in an inverted infection system -
  In order to investigate SARS-CoV-2 mutations and their impact on immune evasion and infectivity, we developed a Deep Mutational Scanning (DMS) platform utilizing an inverted infection assay to measure spike expression, ACE2 affinity, and viral infectivity in human cells. Surprisingly, our analysis reveals that spike protein expression, rather than ACE2 affinity, is the primary factor affecting viral infectivity and correlated with SARS-CoV-2 evolution. Notably, within the N-terminal domain (NTD), spike expression and infectivity-enhancing mutations are concentrated in flexible loops. We also observed that Omicron variants BA.1 and BA.2 exhibit immune evasion through receptor binding domain (RBD) mutations, although these mutations reduce structural stability. Interestingly, the NTD has evolved to increase stability, compensating for the RBD instability and resulting in heightened overall infectivity. Our findings, available in SpikeScanDB, emphasize the importance of spike expression levels and compensatory mutations in both the NTD and RBD domains for shaping Omicron variant infectivity.
  🖺 Full Text HTML: Deep mutational scanning of whole SARS-CoV-2 spike in an inverted infection system
• Breakthrough infection elicits hypermutated IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2 variants including BQ and XBB lineages -
  The rapid emergence of SARS-CoV-2 variants of concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as to inform the development of vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents of breakthrough infection with relatively high neutralizing titers against all tested viruses including BQ and XBB lineages. Among 50 spike-specific monoclonal antibodies (mAbs) cloned from their B cells, the top 6 neutralizing mAbs (KXD01-06) belong to previously defined IGHV3-53/3-66 public antibodies. Although most antibodies in this class are dramatically escaped by VOCs, KXD01-06 exhibit broad neutralizing capacity with the IC50s of KXD01 ranging from 0.011~0.059ug/ml. Deep mutational scanning reveals that KXD01-06 target highly conserved sites on RBD including D420, Y421, L455, F456, A475 and N487. Genetic and functional analysis further indicates that the extent of somatic hypermutation is critical for the breadth of IGHV3-53/3-66 public antibodies. Overall, we discovered and characterized IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2, which provides rationale for novel vaccines and antibody therapeutics based on this class of antibodies.
  🖺 Full Text HTML: Breakthrough infection elicits hypermutated IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2 variants including BQ and XBB lineages
• ACE2 mimetic antibody potently neutralizes all SARS-CoV-2 variants and fully protects in XBB.1.5 challenged monkeys -
  The rapid evolution of SARS-CoV-2 to variants with improved transmission efficiency and reduced sensitivity to vaccine-induced humoral immunity has abolished the protective effect of licensed therapeutic human monoclonal antibodies (mAbs). To fill this unmet medical need and protect vulnerable patient populations, we isolated the P4J15 mAb from a previously infected, vaccinated donor, with <20 ng/ml neutralizing activity against all Omicron variants including the latest XBB.2.3 and EG.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ~93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. Although SARS-CoV-2 mutants escaping neutralization by P4J15 were selected in vitro, these displayed lower infectivity, poor binding to ACE2, and the corresponding "escape" mutations are accordingly rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, we show that P4J15 confers complete prophylactic protection. We conclude that the P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug.
  🖺 Full Text HTML: ACE2 mimetic antibody potently neutralizes all SARS-CoV-2 variants and fully protects in XBB.1.5 challenged monkeys
• A high-throughput multiplex array for antigen-specific serology with automated analysis. -
  The utility of high-throughput systems to evaluate antigen-specific Ab has been highlighted by the SARS-CoV-2 pandemic. Pathogen specific antibody levels are often used to assess protection following vaccination and, in the case of novel pathogens, an indication of prior exposure. Several platforms exist to visualize antigen-specific Ab, however most are not quantitative and difficult to scale for population levels studies. Additionally, the sensitivity across platforms differs making direct comparisons between studies difficult. Cytometric Bead Arrays are an attractive platform for antigen-specific Ab measurements as they allow antibodies reactive against several antigens and of several isotypes to be performed simultaneously. Additionally, cytometric arrays exhibit a high sensitivity and can be designed to provide quantitative measurements. Using commercially available particles, a biotin-Streptavidin loading strategy, and the inclusion of indirect standards, we describe here a flexible system that can be modified to include a variety of antigens. We generated two arrays, one focused on b-Coronavirus antigens and one focused on Influenza. To support the high throughput capacity of this system, we developed a suit of automated tools to process raw data into antigen-reactive IgM, IgA, and IgG. We describe quality control requirements, assay performance, and normalizations to accurately quantitate antigen specific Ig.
  🖺 Full Text HTML: A high-throughput multiplex array for antigen-specific serology with automated analysis.
• The impact of frailty on the outcomes of COVID-19 patients with persistent critical illness: A population-based cohort study. -

  Objectives: Persistent critical illness (PerCI, > or equal to 10 days in Intensive Care Unit [ICU]) is defined as the time from ICU admission when patients antecedent characteristics define their mortality rather than the admission aetiology. Patients with frailty and without COVID-19 have a higher risk of developing and dying from PerCI. We aimed to investigate the impact of frailty on critically ill patients with COVID-19 experiencing PerCI. Methods: We conducted a retrospective multicentre cohort study including 103 Australian and New Zealand ICUs over two years, investigating the impact of frailty, measured with Clinical Frailty Scale (CFS), in patients with COVID-19, between patients with and without PerCI. Results: The prevalence of PerCI was similar between patients with and without frailty (25.4% vs. 27.9%; p=0.44). Hospital mortality was higher in patients with PerCI than without (28.8% vs. 9.3%; p<0.001), with mortality rising with increasing CFS (p<0.001). Frailty independently predicted hospital mortality, but when adjusted for ANZROD and sex, its impact was no different in patients with and without PerCI (odds ratio [OR]=1.30 [95%-CI: 1.14-1.49] vs. OR=1.46 [95%-CI: 1.29-1.64]). Conclusions: The presence of frailty independently predicted hospital mortality in patients with PerCI, but frailty did not have a different impact on patients with and without PerCI.

  🖺 Full Text HTML: The impact of frailty on the outcomes of COVID-19 patients with persistent critical illness: A population-based cohort study.
• The scientific chaos phase of the Great Pandemic: A longitudinal analysis and systematic review of the first surge of clinical research concerning COVID-19 -

  Abstract Background Early stages of catastrophes like COVID-19 are often led by chaos and panic. To characterize the initial chaos phase of clinical research in such situations, we analyzed the first surge of more than 1000 clinical trials about the new disease at baseline and after two years follow-up. Our 3 main objectives were: (1) Assessment of spatial and temporal evolution of clinical research of COVID-19 across the globe, (2) Assessment of transparency and quality - trial registration, (3) Assessment of research waste and redundancies. Methods By entering the keyword “COVID-19” we screened the International Clinical Trials Registry Platform of the WHO and downloaded the search output when our goal of 1000 trials was reached on the 1st of April. Additionally, we verified the integrity of the downloaded data from the meta registry by comparing the data with each individual registration record on their source register. Also, we conducted a follow-up after two years to track their progress. Results (1) The spatial evolution followed the geographical spread of the disease as expected, however, the temporal development suggested that panic was the main driver for clinical research activities. (2) Trial registrations and registers showed a huge lack of transparency by allowing retrospective registrations and not keeping their registration records up to date. Quality of trial registration seems to have improved over the last decade, yet crucial information still was missing. (3) Research waste and redundancies were present as suggested by discontinuation of trials, preventable flaws in study design, and similar but uncoordinated research topics operationally fragmented in isolated silo-structures. Conclusion The scientific response mechanism across the globe was intact during the chaos phase. However, supervision, leadership, and accountability are urgently needed to prevent research waste, to ensure effective structure, quality, and validity to ultimately break the “panic-then-forget” cycle in future catastrophes.

  🖺 Full Text HTML: The scientific chaos phase of the Great Pandemic: A longitudinal analysis and systematic review of the first surge of clinical research concerning COVID-19
• Community-onset urinary tract infection in females in the context of COVID-19: a longitudinal population cohort study exploring case presentation, management, and outcomes -

  Background COVID-19 affected the epidemiology of other infectious diseases and how they were managed. Urinary tract infection (UTI) is one of the most common infections treated in the community in England. We investigated the impact of the COVID-19 pandemic on UTI primary care consultations and outcomes in female patients. Methods and findings We analysed General Practice (GP) consultation and hospital admission records using the Whole Systems Integrated Care (WSIC) data in North West London between 2016 and 2021. We quantified the changes in UTI GP consultation rates using time series analysis before and during the pandemic. We assessed the outcomes of UTI, measured by subsequent bacteraemia and sepsis within 60 days, for consultations delivered face-to-face or remotely, with or without diagnostic tests recommended by the national guidelines, and with or without antibiotic treatment. Between January 2016 and December 2021, we identified 375,859 UTI episodes in 233,450 female patients. Before the COVID-19 pandemic (January 2016-February 2020), the UTI GP consultation rate stayed level at 522.8 cases per 100,000 population per month, with a seasonal pattern of peaking in October. Since COVID-19, (March 2020-December 2021), monthly UTI GP consultations declined when COVID-19 cases surged and rose when COVID-19 case fell. During the pandemic, the UTI consultations delivered face-to-face reduced from 72.0% to 29.4%, the UTI consultations with appropriate diagnostic tests, including urine culture and urinalysis, reduced from 17.3% to 10.4%, and the UTI cases treated with antibiotics reduced from 52.0% to 47.8%. The likelihood of antibiotics being prescribed was not affected by whether the consultation was delivered face-to-face or remotely but associated with whether there was a diagnostic test. Regardless of whether the UTI consultation occurred before or during the pandemic, the absence of antibiotic treatment for UTI is associated with a 10-fold increase in the risk of having bacteraemia or sepsis within 60 days, though the patients who consulted GPs for UTI during the pandemic were older and more co-morbid. Across the study period (January 2016-December 2021), nitrofurantoin remained the first-line antibiotic option for UTI. The percentage of non-prophylactic acute UTI antibiotic prescriptions with durations that exceeded the guideline recommendations was 58.7% before the pandemic, and 49.4% since. This led to 830,522 total excess days of treatment, account for 63.3% of all non-prophylactic acute antibiotics prescribed for UTI. Before the pandemic, excess antibiotic days of UTI drugs had been reducing consistently. However, this decline slowed down during the pandemic. Having a diagnostic test was associated with 0.6 less excess days of antibiotic treatment. Conclusions This analysis provides a comprehensive examination of management and outcomes of community-onset UTI in female patients, considering the changes in GP consultations during the COVID-19 pandemic. Our findings highlighted the importance of appropriate urine testing to support UTI diagnosis in symptomatic patients and initiation of antibiotic treatment with appropriate course duration. Continued monitoring is required to assess the overall impact on patients and health systems from the changed landscape of primary care delivery.

  🖺 Full Text HTML: Community-onset urinary tract infection in females in the context of COVID-19: a longitudinal population cohort study exploring case presentation, management, and outcomes
• COVFlow: performing virus phylodynamics analyses from selected SARS-CoV-2 genome sequences -
  Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
  🖺 Full Text HTML: COVFlow: performing virus phylodynamics analyses from selected SARS-CoV-2 genome sequences
• Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model -
  Home Advantage (HA) is a robust phenomenon in which sport teams or individuals are more successful when they play in front of their fans. There are a number of causes of HA, but most theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. The interest in HA has grown during the Covid-19 pandemic as most competitions were taking place behind closed doors, a perfect control condition for disentangling the causal effects behind HA. Despite the presence of useful conceptual frameworks, most previous research has focused on investigating isolated individual factors. Here we review our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously. HAM assumes that the crowd effects are mediated through other relevant factors, such as referee bias and team performance. Most importantly, HAM can be formally expressed as a mediation model, a technique widely employed in social sciences for investigating causal pathways. We demonstrate how researchers can use HAM to model the HA in European football and how moderating variables, such as Covid-19 and absence of fans, can be incorporated in the model to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, we also provide information about practical implementation of mediation and moderated mediation models in the Bayesian framework. Similar implementations can be adapted for use in other sport science domains.
  🖺 Full Text HTML: Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model
• Identification of predictive patient characteristics for assessing the probability of COVID-19 in-hospital mortality -

  As the world emerges from the COVID-19 pandemic, there is an urgent need to understand patient factors that may be used to predict the occurrence of severe cases and patient mortality. Approximately 20% of SARS-CoV-2 infections lead to acute respiratory distress syndrome caused by the harmful actions of inflammatory mediators. Patients with severe COVID-19 are often afflicted with neurologic symptoms, and individuals with pre-existing neurodegenerative disease have an increased risk of severe COVID-19. Although collectively, these observations point to a bidirectional relationship between severe COVID-19 and neurologic disorders, little is known about the underlying mechanisms. Here, we analyzed the electronic health records of 471 patients with severe COVID-19 to identify clinical characteristics most predictive of mortality. Feature discovery was conducted by training a regularized logistic regression classifier that serves as a machine-learning model with an embedded feature selection capability. SHAP analysis using the trained classifier revealed that a small ensemble of readily observable clinical features, including characteristics associated with cognitive impairment, could predict in-hospital mortality with an accuracy greater than 0.85 (expressed as the area under the ROC curve of the classifier). These findings have important implications for the prioritization of clinical measures used to identify patients with COVID-19 (and, potentially, other forms of acute respiratory distress syndrome) having an elevated risk of death.

  🖺 Full Text HTML: Identification of predictive patient characteristics for assessing the probability of COVID-19 in-hospital mortality
• Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections -

  Background: Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic. Methods: With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis. Results: We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2.05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0.35; 95% CI, 0.35-0.36) and UTI (adjusted OR 0.45; 95% CI, 0.44-0.46), compared to URTI (adjusted OR 1.04; 95% CI, 1.03-1.06). Conclusion: Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks.

  🖺 Full Text HTML: Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections

From Clinical Trials

• Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine
  Sponsor:   PT Bio Farma
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-2;   Biological: SCTV01E
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3) - Condition:   COVID-19
  Interventions:   Drug: theophylline;   Drug: Placebo
  Sponsor:   Washington University School of Medicine
  Recruiting

• Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+ - Condition:   COVID-19
  Intervention:   Device: Resistance Training
  Sponsor:   Józef Piłsudski University of Physical Education
  Recruiting

• Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition:   COVID-19
  Intervention:   Procedure: Lymph node aspiration / Blood sampling
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Multimodal Long Covid19 - Condition:   Long COVID-19 Syndrome
  Intervention:   Other: Multimodal intervention in Long Covid19
  Sponsors:   Universidad de Magallanes;   Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG;   Clinical Hospital Dr. Lautaro Navarro Avaria
  Active, not recruiting

• COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults - Condition:   Covid19
  Interventions:   Biological: MVA-SARS-2-S;   Other: Placebo
  Sponsors:   Universitätsklinikum Hamburg-Eppendorf;   German Center for Infection Research;   Philipps University Marburg Medical Center;   Ludwig-Maximilians - University of Munich;   University Hospital Tuebingen;   CTC-NORTH
  Withdrawn

• Treatment of Long COVID (TLC) Feasibility Trial - Condition:   COVID-19
  Interventions:   Drug: Low-dose Naltrexone (LDN);   Drug: Cetirizine;   Drug: Famotidine;   Drug: LDN Placebo;   Drug: Cetirizine Placebo;   Drug: Famotidine Placebo
  Sponsors:   Emory University;   CURE Drug Repurposing Collaboratory (CDRC)
  Not yet recruiting

• Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease - Conditions:   COVID-19;   Renal Insufficiency, Chronic
  Intervention:   Drug: Nirmatrelvir/ritonavir
  Sponsor:   Chinese PLA General Hospital
  Recruiting

• Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS). - Conditions:   Post-Acute COVID-19 Syndrome;   Cognitive Impairment;   Neurological Complication
  Intervention:   Drug: VIX001
  Sponsor:   Neobiosis, LLC
  Not yet recruiting

• A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression - Conditions:   COVID 19 Disease;   Mild to Moderate COVID 19 Disease;   SARS-CoV-2;   Infectious Disease;   Severe Acute Respiratory Syndrome Coronavirus 2
  Interventions:   Drug: Tafenoquine Oral Tablet;   Drug: Placebo
  Sponsor:   60P Australia Pty Ltd
  Not yet recruiting

• A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients - Condition:   Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)
  Interventions:   Drug: MBS-COV;   Drug: Placebo
  Sponsor:   Oneness Biotech Co., Ltd.
  Not yet recruiting

• Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19 - Conditions:   Asthenia;   COVID-19;   Functional MRI;   Cognitive Impairment
  Interventions:   Other: Structural and functional MRI;   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• NDV-HXP-S Vaccine Clinical Trial (COVIVAC) - Condition:   COVID-19
  Intervention:   Biological: COVIVAC vaccine
  Sponsors:   Institute of Vaccines and Medical Biologicals, Vietnam;   National Institute of Hygiene and Epidemiology (NIHE), Vietnam;   Center for Disease Control of Thai Binh Province, Vietnam
  Completed

• Study of AZD3152 Intramuscular Injection or Intravenous Infusion in Healthy Japanese Adult Participants - Condition:   COVID-19, SARS-CoV-2
  Interventions:   Biological: AZD3152 (Cohort 1);   Biological: Placebo (Cohort 1);   Biological: AZD3152 (Cohort 2);   Biological: Placebo (Cohort 2);   Biological: AZD3152 (Cohort 3);   Biological: Placebo (Cohort 3)
  Sponsor:   AstraZeneca
  Not yet recruiting

From PubMed

• Modulation of NRF2: biological dualism in cancer, targets and possible therapeutic applications - SIGNIFICANCE: The NRF2-KEAP1 system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases,, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging.

• Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia - Purpose As a public health emergency of international concern, the coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia….

• Research Progress of Immunomodulation on Anti-COVID-19 and the Effective Components from Traditional Chinese Medicine - SARS-CoV-2 has posed a threat to the health of people around the world because of its strong transmission and high virulence. Currently, there is no specific medicine for the treatment of COVID-19. However, for a wide variety of medicines used to treat COVID-19, traditional Chinese medicine (TCM) plays a major role. In this paper, the effective treatment of COVID-19 using TCM was consulted first, and several Chinese medicines that were frequently used apart from their huge role in treating it…

• A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf - New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf™; NCT05238675) assessing the efficacy and safety…

• Immunogenicity and safety of inactivated SARS-CoV-2 vaccine in haemodialysis patients: a prospective cohort study - End-stage renal disease patients on haemodialysis (HD) have been largely excluded from SARS-CoV-2 vaccine trials due to safety reasons and shown to mount lower responses to vaccination. This study aims to evaluate the immunogenicity and safety of inactivated COVID-19 vaccine among HD patients compared to healthy controls. All subjects who received the primary inactivated COVID-19 vaccination had their blood samples tested 21 days after the second dose. We report the immunogenicity based on…

• Effective SARS-CoV-2 replication of monolayers of intestinal epithelial cells differentiated from human induced pluripotent stem cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe acute respiratory symptoms in humans. Controlling the coronavirus disease pandemic is a worldwide priority. The number of SARS-CoV-2 studies has dramatically increased, and the requirement for analytical tools is higher than ever. Here, we propose monolayered-intestinal epithelial cells (IECs) derived from human induced pluripotent stem cells (iPSCs) instead of three-dimensional cultured intestinal organoids as a suitable…

• Picolinic acid is a broad-spectrum inhibitor of enveloped virus entry that restricts SARS-CoV-2 and influenza A virus in vivo - The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and…

• Federal telehealth policy changes during the COVID-19 public health emergency: Associations with telemental health use among rural and urban Medicare beneficiaries - CONCLUSIONS: TMH mitigated PHE-related barriers to MHS access for rural and urban beneficiaries, but urban residents benefited disproportionately. Among rural beneficiaries, older age was related to lower TMH use. To avoid reinforcing existing MHS access disparities, policies must address factors limiting TMH use among rural beneficiaries, especially those over 75 and those from historically underserved communities.

• SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection - A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify…

• Seasonal coronavirus infections trigger NLRP3 inflammasome activation in macrophages but is therapeutically targetable - Seasonal coronaviruses widely circulate in the global population, and severe complications can occur in specific vulnerable populations. Little is known on their pathogenic mechanisms and no approved treatment is available. Here, we present anecdotal evidence that the level of IL-1β, a hallmark of inflammasome activation, appears elevated in a subset of seasonal coronavirus infected patients. We found that cultured human macrophages support the full life cycle of three cultivatable seasonal…

• Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response - Early in the COVID-19 pandemic, data suggested that males had a higher risk of developing severe disease and that androgen deprivation therapy might be associated with protection. Combined with the fact that TMPRSS2 (transmembrane serine protease 2), a host entry factor for the SARS-CoV-2 virus, was a well-known androgen-regulated gene, this led to an upsurge of research investigating androgen receptor (AR)-targeting drugs. Proxalutamide, an AR antagonist, was shown in initial clinical studies…

• Exploring epigenetic drugs as potential inhibitors of SARS-CoV-2 main protease: a docking and MD simulation study - The COVID-19 pandemic has caused havoc around the globe since 2019 and is considered the largest global epidemic of the twentieth century. Although the first antiviral drug, Remdesivir, was initially introduced against COVID‑19, virtually no tangible therapeutic drugs exist to treat SARS-CoV-2 infection. FDA-approved Paxlovid (Nirmatrelvir supplemented by Ritonavir) was recently announced as a promising drug against the SARS-CoV-2 major protease (M^(pro)). Here we report for the first time the…

• Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B - Artemisia annua is the plant that produces artemisinin, an endoperoxide-containing sesquiterpenoid used for the treatment of malaria. A. annua extracts, which contain other bioactive compounds, have been used to treat other diseases, including cancer and COVID-19, the disease caused by the virus SARS-CoV-2. In this study, a methyl ester derivative of arteannuin B was isolated when A. annua leaves were extracted with a 1:1 mixture of methanol and dichloromethane. This methyl ester was thought to…

• M^pro-targeted anti-SARS-CoV-2 inhibitor-based drugs - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global health emergency. The main protease is an important drug target in coronaviruses. It plays an important role in the processing of viral RNA-translated polyproteins and is highly conserved in the amino acid sequence and three-dimensional structure, making it a good drug target for which several small molecule inhibitors are available. This paper describes the various anti-severe acute respiratory syndrome…

• New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19 - More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit “post-COVID-19 symptoms,” which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase…

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