Covid-19 Sentry

Contents

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

From Preprints

• The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model -

  SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics - Virus Spread model (PeDViS): an individual-based model that combines pedestrian behaviour models with virus spread models that incorporate direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place, and compared this to benchmark at risk interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to build-up of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent. This uncertainty should be considered when assessing transmission risks upon different types of human interactions in indoor spaces. We illustrated the multi-dimensionality of indoor SARS-CoV-2 transmission that emerges from the interplay of human behaviour and the spread of respiratory viruses. A modelling strategy that incorporates this in risk assessments can help inform policy makers and citizens on the safe use of indoor spaces with varying inter-human interactions.

  🖺 Full Text HTML: The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces: Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model
• How can selective processing of vaccination information be diminished? Effects of mindsets and kinds of information -
  Background: Selective processing of attitude-consistent information is a substantial obstacle in convincing vaccine-skeptical people of the benefits of vaccinations. This study tests (i) which types of information are particularly prone to such selective information processing, and (ii) whether a deliberative (vs. implemental) mindset focusing on potential benefits and harms may diminish its effects. Design: 612 Mturk participants were randomized into an implemental or deliberative mindset and received a flu vaccine-skeptical narrative, a flu vaccination facts box transparently summarizing risks and benefits, and a message by the Center for Disease Prevention and Control (CDC) in favor of the flu vaccine either referring to COVID-19 or not. We tested how these variations affected the acceptance of and the willingness to share each message. Furthermore, we evaluated their impact on flu vaccination attitudes and intentions. Results: The mindset manipulation failed to diminish generally prevalent selective information processing. While vaccine-skeptics did not accept and like the CDC message referring to COVID-19 (particularly in a deliberative mindset), they generally accepted the vaccination facts box more readily compared to both CDC messages. Conclusion: While mindsets were ineffective, more general and transparent information may be more likely to reach an anti-vaccine audience.
  🖺 Full Text HTML: How can selective processing of vaccination information be diminished? Effects of mindsets and kinds of information
• Predicting Depression and Anxiety Among Adults with Disabilities During the COVID-19 Pandemic -
  Purpose/Objective: Emerging research has highlighted sources of magnified stress and trauma for people with disabilities during the COVID-19 pandemic, as compared to others in the general population. However, little research has examined the mental health impact of the pandemic on people with disabilities in relation to disability-related stigma, social isolation, and demographic characteristics. The present study therefore sought to identify predictors of depression and anxiety symptoms among U.S. adults with disabilities during the COVID-19 pandemic. Research Methods/Designs: Data were collected online between October and December 2020. U.S. adults with disabilities (n = 441) completed self-report measures of depression, anxiety, psychosocial processes, and a range of demographic and disability characteristics. Results: In our sample, 61.0% and 50.0% of participants met criteria for a probable diagnosis of major depressive disorder and generalized anxiety disorder, respectively. Participants also experienced significantly higher levels of disability-related stigma and social isolation compared to pre-pandemic norms. Hierarchical regression analyses identified higher social isolation, presence of chronic pain, younger age, higher disability-related stigma, and higher worries about contracting COVID-19 as significant predictors of both depression and anxiety symptoms. Conclusion/implications: This study highlights important demographic and psychosocial predictors of mental health risks for people with disabilities in the context of COVID-19. Findings further underscore the need to attend to those at elevated risk within the disability community as rehabilitation professionals, disability organizations, and policymakers work to support people with disabilities in post-pandemic recovery and create a more equitable response to ongoing and future public health crises.
  🖺 Full Text HTML: Predicting Depression and Anxiety Among Adults with Disabilities During the COVID-19 Pandemic
• Narrative identity among people with disabilities during the COVID-19 pandemic: The interdependent self -
  This study examines narrative identity among a large, diverse (American) sample of people with disabilities (PWDs) during the “second wave” of the COVID-19 pandemic (October-December, 2020). The study relied on abductive analyses, combining a purely inductive phase of inquiry followed by two rounds of investigation that filtered inductive insights through three theoretical lenses: social-ecological theory, the theory of narrative identity, and perspectives from the interdisciplinary field of disability studies. The central result was the identification of a particular configuration of self, one that was demonstrably interdependent with both immediate interpersonal contexts and with broader cultural contexts. This interdependent self was interpreted in both positive and negative ways by PWDs. These findings invite future inquiry into commonplace conceptualizations of an independent self at the center of personality research.
  🖺 Full Text HTML: Narrative identity among people with disabilities during the COVID-19 pandemic: The interdependent self
• Design of SARS-CoV-2 protease inhibitors with improved affinity and reduced sensitivity to mutations -
  Inhibitors of the SARS-CoV-2 main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function on these mutants are thus urgently needed. We hypothesized that the covalent HCV protease inhibitor boceprevir (BPV) could serve as the basis for orally bioavailable drugs that inhibit SARS-CoV-2 Mpro more tightly than existing drugs. Performing structure-guided modifications of BPV, we developed a picomolar-affinity inhibitor, ML2006a4, with antiviral activity, oral pharmacokinetics, and therapeutic efficacy similar or superior to NTV. A crucial feature of ML2006a4 is a novel derivatization of the ketoamide reactive group that improves cell permeability and oral bioavailability. Finally, ML2006a4 is less sensitive to several mutations that cause resistance to NTV or ETV and occur in the natural SARS-CoV-2 population. Thus, anticipatory drug design can preemptively address potential resistance mechanisms.
  🖺 Full Text HTML: Design of SARS-CoV-2 protease inhibitors with improved affinity and reduced sensitivity to mutations
• Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting -
  The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
  🖺 Full Text HTML: Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting
• Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease -
  Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1- deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.
  🖺 Full Text HTML: Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease
• Faith and Outgroup Dehumanization During COVID -
  We explore how Christians and Buddhists, of different religiosity, react to death within the context of the Covid-19 pandemic. Previous research has found that the interaction between cultural level, individual level and situational level factors are necessary to consider for a more comprehensive grasp of a phenomenon. We look at how Religion x Religiosity x Threat of Covid interact and show different relationships between these variables and dehumanization. We find that at higher levels of disruption by Covid-19 on religious practice (but not lower levels), Christians high on extrinsic religiosity (but low on intrinsic religiosity) dehumanized religious outgroups the most, whereas Christians high on extrinsic and high on intrinsic religiosity dehumanized religious outgroups significantly less. At low levels of impact of Covid-19 on religious practice, only higher levels of extrinsic religiosity were related to higher levels of dehumanization. Buddhists, regardless of level of religiosity and impact of Covid-19 to religious practice, consistently showed a relatively low level of dehumanization against religious outgroups. Findings are triangulated through multiple sources of data and further elaborated through qualitative coding of open-ended responses. These enactment patterns contribute to the religion and terror management literature and offer insights for potentially developing inclusive understanding with outgroup members.
  🖺 Full Text HTML: Faith and Outgroup Dehumanization During COVID
• Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US -

  Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although there are large uncertainties in our predictions, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to narrow uncertainties in future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.

  🖺 Full Text HTML: Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US
• Application of Machine Learning in Prediction of COVID-19 Diagnosis for Indonesian Healthcare Workers -

  The COVID-19 pandemic poses a heightened risk to health workers, especially in low-and middle-income countries such as Indonesia. Due to the limitations of implementing mass RT-PCR testing for health workers, high-performing and cost-effective methodologies must be developed to help identify COVID-19 positive health workers and protect the spearhead of the battle against the pandemic. This study aimed to investigate the application of machine learning classifiers to predict the risk of COVID-19 positivity (by RT-PCR) using data obtained from a survey specific to health workers. Machine learning tools can enhance COVID-19 screening capacity in high-risk populations such as health workers in environments where cost is a barrier to the accessibility of adequate testing and screening supplies. We built two sets of COVID-19 Likelihood Meter (CLM) models: one trained on data from a broad population of health workers in Jakarta and Semarang (full model) and tested on the same, and one trained on health workers from Jakarta only (Jakarta model) and tested on both the same and an independent population of Semarang health workers. The area under the receiver-operating-characteristic curve (AUC), average precision (AP), and the Brier score (BS) were used to assess model performance. Shapely additive explanations (SHAP) were used to analyse future importance. The final dataset for the study included 5,393 healthcare workers. For the full model, the random forest was selected as the algorithm choice. It achieved cross-validation of mean AUC of 0.832 ± 0.015, AP of 0.513 ± 0.039, and BS of 0.124 ± 0.005, and was high performing during testing with AUC and AP of 0.849 and 0.51, respectively. The random forest classifier also displayed the best and most robust performance for the Jakarta model, with AUC of 0.856 ± 0.015, AP of 0.434 ± 0.039, and BS of 0.08 ± 0.0003. The performance when testing on the Semarang healthcare workers was AUC of 0.745 and AP of 0.694. Meanwhile, the performance for Jakarta 2022 test set was an AUC of 0.761 and AP of 0.535. Our models yielded high predictive performance and can be used as an alternative COVID-19 methodology for healthcare workers in Indonesia, therefore helping in predicting an increased trend of transmission during the transition into endemic.

  🖺 Full Text HTML: Application of Machine Learning in Prediction of COVID-19 Diagnosis for Indonesian Healthcare Workers
• Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors -
  Emerging variants of concern of SARS-CoV-2 can significantly reduce the prophylactic and therapeutic efficacy of vaccines and neutralizing antibodies due to mutations in the viral genome. Targeting cell host factors required for infection provides a complementary strategy to overcome this problem since the host genome is less susceptible to variation during the life span of infection. The enzymatic activities of the endosomal PIKfyve phosphoinositide kinase and the serine protease TMPRSS2 are essential to meditate infection in two complementary viral entry pathways. Simultaneous inhibition in cultured cells of their enzymatic activities with the small molecule inhibitors apilimod dimesylate and nafamostat mesylate synergistically prevent viral entry and infection of native SARS-CoV-2 and vesicular stomatitis virus (VSV)-SARS-CoV-2 chimeras expressing the SARS-CoV-2 surface spike (S) protein and of variants of concern. We now report prophylactic prevention of lung infection in mice intranasally infected with SARS-CoV-2 beta by combined intranasal delivery of very low doses of apilimod dimesylate and nafamostat mesylate, in a formulation that is stable for over 3 months at room temperature. Administration of these drugs up to 6 hours post infection did not inhibit infection of the lungs but substantially reduced death of infected airway epithelial cells. The efficiency and simplicity of formulation of the drug combination suggests its suitability as prophylactic or therapeutic treatment against SARS-CoV-2 infection in households, point of care facilities, and under conditions where refrigeration would not be readily available.
  🖺 Full Text HTML: Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors
• No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study. -
  COVID continues to be a major international public health concern, the underlying mechanisms of which are not fully understood. Recent studies suggest that COVID may cause prolonged inflammation within the central nervous system. However, the evidence so far has been limited to few small-scale case studies. To address this, this study leveraged a longitudinal dataset from the UK Biobank that included neuroimaging data prior to and following COVID testing (analytic N=416 including n=224 COVID-positive cases) and applied a novel and non-invasive Diffusion Basis Spectrum Imaging (DBSI) technique to derive putative indices of neuroinflammation (i.e., restricted fraction; DBSI-RF) for gray matter structures and white matter tracts in the brain. We hypothesized that SARS-CoV-2 infection would be associated with elevated DBSI markers of putative neuroinflammation and conducted linear regression analyses with adjustment for age, sex, race, body mass index, smoking frequency, and data acquisition interval. After multiple testing correction using false discovery rate, we found no evidence that COVID is associated with variability in neuroinflammation. Several brain regions showed nominally significant differences in DBSI-RF between COVID cases and controls including psychopathology-related regions linked that are either part of (i.e., orbitofrontal cortex) or functionally connected to the olfactory network (e.g., amygdala, caudate). It remains possible that there are acute and transitory neuroinflammatory effects associated with COVID that were not observed in our study due to potential resolution of COVID prior to the scan. Future research is warranted to examine whether neuroinflammation is associated with SARS-CoV-2 infection in a time- and/or symptom-dependent manner.
  🖺 Full Text HTML: No evidence for the association between COVID-19 and neuroinflammation: A diffusion basis spectrum imaging study.
• Structure, Dynamics and Free Energy Studies on the Effect of Spot Mutations on SARS-CoV-2 Spike Protein Binding with ACE2 Receptor -
  The ongoing COVID-19 pandemic continues to infect people worldwide, and the virus continues to evolve in significant ways which can pose challenges to the efficiency of available vaccines and therapeutic drugs and cause future pandemic. Therefore, it is important to investigate the binding and interaction of ACE2 with different RBD variants. A comparative study using all-atom MD simulations was conducted on ACE2 binding with 8 different RBD variants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N and N501Y-E484K-K417N on RBD. Based on the RMSD, RMSF, and DSSP results, the overall the binding of RBD variants with ACE2 is stable, and the secondary structure of RBD and ACE2 are consistent after the spot mutation. Besides that, a similar buried surface area, a consistent binding interface and a similar amount of hydrogen bonds formed between RBD with ACE2 although the exact residue pairs on the binding interface were modified. The change of binding free energy from spot mutation was predicted using the free energy perturbation (FEP) method. It is found that N501Y, N439K, and K417N can strengthen the binding of RBD with ACE2, while E484K and P479S weaken the binding, and S477N and T478I have negligible effect on the binding. Spot mutations modified the dynamic correlation of residues in RBD based on the dihedral angle covariance matrix calculation. Doing dynamic network analysis, a common intrinsic network community extending from the tail of RBD to central, then to the binding interface region was found, which could communicate the dynamics in the binding interface region to the tail thus to the other sections of S protein. The result can supply unique methodology and molecular insight on studying the molecular structure and dynamics of possible future pandemics and design novel drugs.
  🖺 Full Text HTML: Structure, Dynamics and Free Energy Studies on the Effect of Spot Mutations on SARS-CoV-2 Spike Protein Binding with ACE2 Receptor
• 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

From Clinical Trials

• 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

• 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
  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

• PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition:   SARS-CoV-2
  Interventions:   Drug: Upamostat;   Drug: Placebo (PO)
  Sponsors:   Henry M. Jackson Foundation for the Advancement of Military Medicine;   Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies;   FHI Clinical, Inc.;   RedHill Biopharma Limited
  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

• Immunoadsorption vs. Sham Treatment in Post COVID Patients With Chronic Fatigue Syndrome - Conditions:   Fatigue;   Post-Acute COVID-19 Syndrome
  Intervention:   Procedure: Immunoadsorption vs. sham immunoadsorption
  Sponsor:   Hannover Medical School
  Not yet recruiting

• MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention - Conditions:   Post COVID-19 Condition;   Somatic Symptom Disorder
  Interventions:   Behavioral: yoga;   Behavioral: social contact
  Sponsor:   Medical University Innsbruck
  Recruiting

• Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics - Condition:   Respiratory Viral Infection
  Interventions:   Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel;   Diagnostic Test: BioFire Respiratory Panel 2.1
  Sponsor:   AusDiagnostics Pty Ltd.
  Not yet recruiting

• Expressive Interviewing Agents to Support Health-Related Behavior Change - Condition:   Mental Stress
  Intervention:   Other: Expressive Interviewing
  Sponsors:   University of Michigan;   University of Texas at Austin
  Completed

From PubMed

• Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…

• A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…

• Effects of Sulforaphane on SARS‑CoV‑2 infection and NF‑κB dependent expression of genes involved in the COVID‑19 ‘cytokine storm’ - Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines, the development of specific antiviral agents targeting the SARS‑CoV‑2 life cycle with high efficiency, and/or interfering with the associated ‘cytokine storm’, is highly required. A recent study, conducted by the authors’…

• New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System - All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of β-coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of…

• Development of nanozymes for promising alleviation of COVID-19-associated arthritis - The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like…

• Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter - Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were…

• New cyclic arylguanidine scaffolds as a platform for development of antimicrobial and antiviral agents - According to WHO, infectious diseases are still a significant threat to public health. The combine effects of antibiotic resistance, immunopressure, and mutations within the bacterial and viral genomes necessitates the search for new molecules exhibiting antimicrobial and antiviral activities. Such molecules often contain cyclic guanidine moiety. As part of this work, we investigated the selected antimicrobial and antiviral activity of compounds from the cyclic arylguanidine group. Molecules…

• C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds…

• 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…

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