Covid-19 Sentry

Contents

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

From Preprints

• Integrating T-cell receptor and transcriptome for large-scale single-cell immune profiling analysis -
  Recent advancements in single-cell immune profiling that enable the measurement of the transcriptome and T-cell receptor (TCR) sequences simultaneously have emerged as a promising approach to study immune responses at cellular resolution. Yet, combining these different types of information from multiple datasets into a joint representation is complicated by the unique characteristics of each modality and the technical effects between datasets. Here, we present mvTCR, a multimodal generative model to learn a unified representation across modalities and datasets for joint analysis of single-cell immune profiling data. We show that mvTCR allows the construction of large-scale and multimodal T-cell atlases by distilling modality-specific properties into a shared view, enabling unique and improved data analysis. Specifically, we demonstrated mvTCR’s potential by revealing and separating SARS-CoV-2-specific T-cell clusters from bystanders that would have been missed in individual unimodal data analysis. Finally, mvTCR can enable automated analysis of new datasets when combined with transfer-learning approaches. Overall, mvTCR provides a principled solution for standard analysis tasks such as multimodal integration, clustering, specificity analysis, and batch correction for single-cell immune profiling data.
  🖺 Full Text HTML: Integrating T-cell receptor and transcriptome for large-scale single-cell immune profiling analysis
• Erroneous Consonance. How Inaccurate Beliefs about Physician Opinion Influence COVID-19 Vaccine Hesitancy -
  Throughout the COVID-19 pandemic, researchers have studied how Americans’ attitudes toward health experts influence their health behaviors and policy opinions. Fewer, however, consider the potential gap between individual and expert opinion about COVID-19, and how that might shape health attitudes and behavior. This omission is notable, as discrepancies between individual and expert opinion could help explain why some Americans fail to take action to protect themselves and others from the virus. In novel demographically representative surveys of the US adult population (N = 5,482) and primary care physician subpopulations (PCPs; N = 625), we contrast the relationship between: (1) Americans’ and (2) PCPs’ preferences regarding who ought to be responsible for taking action to combat the spread of COVID-19, as well as (3) Americans’ perceptions of PCP preferences (“PCP meta-opinion”). In the aggregate, we find that Americans are far less likely than PCPs to see a role for both private and state actors in taking action to combat COVID-19. Interestingly, though, this disjuncture is not reflected in individual-level PCP meta-opinion; as most Americans think that PCPs share their views on state and private intervention (𝛕b = 0.44 - 0.49). However, this consonance is often erroneous, which we show can have problematic health consequences. Multivariate models suggest that Americans who both see little place for individual responsibility in taking action to stop viral spread and who think that PCPs share those views are significantly less likely to vaccinate against COVID-19. We conclude by discussing the public health benefits of efforts to bring public opinion in line with expert opinion.
  🖺 Full Text HTML: Erroneous Consonance. How Inaccurate Beliefs about Physician Opinion Influence COVID-19 Vaccine Hesitancy
• Comparative Effectiveness of Dexamethasone in Treatment of Hospitalized COVID-19 Patients during the First Year of the Pandemic: The N3C Data Repository -

  Background Dexamethasone, a widely available glucocorticoid, was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial; however, evidence is still needed to support its real-world effectiveness in patients with a wide range of comorbidities and in diverse care settings. Objectives To conduct a comparative effectiveness analysis of dexamethasone use with and without remdesivir in hospitalized COVID-19 patients using electronic health record data. Methods We conducted a retrospective real-world effectiveness analysis using the harmonized, highly granular electronic health record data of the National COVID Cohort Collaborative (N3C) Data Enclave. Analysis was restricted to COVID-19 patients in an inpatient setting, prior to vaccine availability. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome as defined by use of ECMO or mechanical ventilation during stay. Missing data were imputed with single imputation. Matching of dexamethasone-treated patients to non-dexamethasone-treated controls was accomplished using propensity score (PS) matching, stratified by remdesivir treatment and based on demographics, baseline laboratory values, and comorbidities. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS. Results Regression analysis revealed a statistically significant association between dexamethasone use and reduced risk of in-hospital mortality for those not receiving remdesivir (OR=0.77, 95% CI: 0.62 to 0.95, p=0.017), and a borderline statistically significant risk for those receiving remdesivir (OR=0.74, 95% CI: 0.53 to 1.02, p=0.054). Treatment also showed secondary outcome benefit. In sensitivity analyses, treatment effect size generally remained similar with some heterogeneity of benefit across strata of PS. Conclusions We add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.

  🖺 Full Text HTML: Comparative Effectiveness of Dexamethasone in Treatment of Hospitalized COVID-19 Patients during the First Year of the Pandemic: The N3C Data Repository
• ViReaDB: A user-friendly database for compactly storing viral sequence data and rapidly computing consensus genome sequences -
  Motivation: In viral molecular epidemiology, reconstruction of consensus genomes from sequence data is critical for tracking mutations and variants of concern. However, storage of the raw sequence data can become prohibitively large, and computing consensus genome from sequence data can be slow and requires bioinformatics expertise. Results: ViReaDB is a user-friendly database system for compactly storing viral sequence data and rapidly computing consensus genome sequences. From a dataset of 1 million trimmed mapped SARS-CoV-2 reads, it is able to compute the base counts and the consensus genome in 16 minutes, store the reads alongside the base counts and consensus in 50 MB, and optionally store just the base counts and consensus (without the reads) in 300 KB. Availability: ViReaDB is freely available on PyPI (https://pypi.org/project/vireadb) and on GitHub (https://github.com/niemasd/ViReaDB) as an open-source Python software project.
  🖺 Full Text HTML: ViReaDB: A user-friendly database for compactly storing viral sequence data and rapidly computing consensus genome sequences
• Sensitivity of endemic behaviour of Covid-19 under a multi-dose vaccination regime, to various biological parameters and control variables -

  For an infectious disease such as Covid-19, we present a new four-stage vaccination model (un-vaccinated, dose 1+2, booster, repeated boosters), which examines the impact of vaccination coverage, vaccination rate, generation interval, control reproduction number, vaccine efficacies, and rates of waning immunity, upon the dynamics of infection. We derive a single equation that allows computation of equilibrium prevalence and incidence of infection, given knowledge about these parameter and variable values. Based upon a 20 compartment model, we develop a numerical simulation of the associated differential equations. The model is not a forecasting or even predictive one, given the uncertainty about several biological parameter values. Rather, it is intended to aid qualitative understanding of how equilibrium levels of infection may be impacted upon, by the parameters of the system. We examine one at a time sensitivity analysis around a base case scenario. The key finding which should be of interest to policy makers, is that while factors such as improved vaccine efficacy, increased vaccination rates, lower waning rates, and more stringent non- pharmaceutical interventions might be thought to improve equilibrium levels of infection, this might only be done to good effect, if vaccination coverage on a recurrent basis, is sufficiently high.

  🖺 Full Text HTML: Sensitivity of endemic behaviour of Covid-19 under a multi-dose vaccination regime, to various biological parameters and control variables
• Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis -

  Background: The COVID–19 pandemic has negatively impacted the social fabric of people with multiple sclerosis (pwMS). Objective: To evaluate the associations between personal social network environment and neurological function in pwMS and controls during the COVID–19 pandemic and compare with the pre–pandemic baseline. Methods: We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID–19 pandemic (March–December 2020). We then leveraged data collected between 2017–2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a questionnaire that quantified the structure and composition of their personal social network, including the health behaviors of network members. We assessed neurological disability using three interrelated patient–reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale–Revised (MSRS–R), and Patient Reported Outcomes Measurement Information System (PROMIS)–Physical Function. We identified the network features associated with neurologic disability using paired t–tests and covariate–adjusted regressions. Results: In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, higher percent of network members with a perceived negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in controls (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the percent of people contacted “weekly or less” (p<.001) decreased during the COVID-19 pandemic for both pwMS (30.34% to 18.78%) and controls (23.48% to 14.89%) when compared to the pre-pandemic period. PwMS further experienced a greater reduction in network size (p<.001), increase in constraint (a measure of close ties of the network, p<.001) and decrease in maximum degree (highest number of ties of a network member, p<.001) than controls during the COVID–19 pandemic. These changes in network features were not associated with worsening neurological disability during the pandemic. Conclusions: Our findings suggest that negative health influences in personal social networks are associated with worse disability in all participants, and the COVID–19 pandemic led to contraction of personal social networks to a greater extent for pwMS than controls.

  🖺 Full Text HTML: Impact of the COVID-19 Pandemic on Personal Networks and Neurological Outcomes of People with Multiple Sclerosis: A Case-Control Cross-sectional and Longitudinal Analysis
• Inequalities in children’s mental health care: analysis of routinely collected data on prescribing and referrals to secondary care -

  Background One in eight children in the United Kingdom are estimated to have a mental health condition, and many do not receive support or treatment. The COVID-19 pandemic has negatively impacted mental health and disrupted the delivery of care. Prevalence of poor mental health is not evenly distributed across age groups, by sex or socioeconomic groups. Equity in access to mental health care is a policy priority but detailed socio-deomgraphic trends are relatively under-researched. Methods We analysed records for all mental health prescriptions and referrals to specialist mental health outpatient care between the years of 2015 and 2021 for children aged 2 to 17 years in a single NHS Scotland health board region. We analysed trends in prescribing, referrals, and acceptance to out-patient treatment over time, and measured differences in treatment and service use rates by age, sex, and area deprivation. Results We identified 18,732 children with 178,657 mental health prescriptions and 21,874 referrals to specialist outpatient care. Prescriptions increased by 59% over the study period. Boys received double the prescriptions of girls and the rate of prescribing in the most deprived areas was double that in the least deprived. Mean age at first mental health prescription was almost 1 year younger in the most deprived areas than in the least. Referrals increased 9% overall. Initially, boys and girls both had an annual referral rate of 2.7 per 1,000, but this fell 6% for boys and rose 25% for girls. Referral rate for the youngest decreased 67% but increased 21% for the oldest. The proportion of rejected referrals increased steeply since 2020 from 17% to 30%. The proportion of referrals accepted for girls rose to 62% and the mean age increased 1.5 years. Conclusions The large increase in mental health prescribing and changes in referrals to specialist outpatient care aligns with emerging evidence of increasing poor mental health, particularly since the start of the COVID-19 pandemic. The static size of the population accepted for specialist treatment amid greater demand, and the changing demographics of those accepted, indicate clinical prioritisation and unmet need. Persistent inequities in mental health prescribing and referrals require urgent action.

  🖺 Full Text HTML: Inequalities in children’s mental health care: analysis of routinely collected data on prescribing and referrals to secondary care
• Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants -
  The COVID-19 pandemic has highlighted how viral variants that escape monoclonal antibodies can limit options to control an outbreak. With the emergence of the SARS-CoV-2 Omicron variant, many clinically used antibody drug products lost in vitro and in vivo potency, including AZD7442 and its constituent, AZD1061. Rapidly modifying such antibodies to restore efficacy to emerging variants is a compelling mitigation strategy. We therefore sought to computationally design an antibody that restores neutralization of BA.1 and BA.1.1 while simultaneously maintaining efficacy against SARS-CoV-2 B.1.617.2 (Delta), beginning from COV2-2130, the progenitor of AZD1061. Here we describe COV2-2130 derivatives that achieve this goal and provide a proof-of-concept for rapid antibody adaptation addressing escape variants. Our best antibody achieves potent and broad neutralization of BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4, BA.5, and BA.5.5 Omicron subvariants, where the parental COV2-2130 suffers significant potency losses. This antibody also maintains potency against Delta and WA1/2020 strains and provides protection in vivo against the strains we tested, WA1/2020, BA.1.1, and BA.5. Because our design approach is computational - driven by high-performance computing-enabled simulation, machine learning, structural bioinformatics and multi-objective optimization algorithms - it can rapidly propose redesigned antibody candidates aiming to broadly target multiple escape variants and virus mutations known or predicted to enable escape.
  🖺 Full Text HTML: Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants
• Safeguarding People against Social Media Frauds during the COVID-19 Oxygen Supply Crisis in India -
  During the second wave of the COVID-19 pandemic in India, the drastic increase in the number of COVID cases led to a positive demand shock for medical grade oxygen. However, an inadequate supply of oxygen created a huge supply-demand gap, making people resort to social media platforms in search of oxygen cylinders for their next of kin. While it alleviated problems for the masses, these desperate posts for oxygen attracted fraudsters, resulting in numerous people not getting oxygen on time. In this paper, we present research problems that arise from this crisis and argue that deep learning can be instrumental towards their solutions. Also, we propose a graph deep learning?based framework to elucidate a possible solution and incite further research in the domain.
  🖺 Full Text HTML: Safeguarding People against Social Media Frauds during the COVID-19 Oxygen Supply Crisis in India
• The ACE-2 receptor accelerates but is not biochemically required for SARS-CoV-2 membrane fusion. -
  The SARS-CoV-2 coronavirus infects human cells via the ACE-2 receptor. Circumstantial evidence suggests that ACE-2 may not just serve as an attachment factor but also help activate the SARS-CoV-2 spike protein for membrane fusion. Here, we test that hypothesis directly, using DNA-lipid tethering as a synthetic attachment factor in the place of ACE-2. We find that SARS-CoV-2 pseudovirus and virus-like particles are both capable of membrane fusion if attached in the absence of ACE-2 and activated with an appropriate protease. However, addition of soluble ACE-2 speeds the fusion reaction. This is observed for both the Wuhan strain and the B.1.1.529 Omicron variant. Kinetic analysis suggests that there are at least two rate-limiting steps for SARS-CoV-2 membrane fusion, one of which is ACE-2 dependent and one of which is not. These data establish that, in the presence of an alternative attachment factor, ACE-2 is not biochemically required for SARS-CoV-2 membrane fusion. Since ACE-2 serves as the high-affinity attachment factor on human cells, the possibility to replace it with other factors has implications for the evolvability of SARS-CoV-2 and the fitness landscape for future related coronaviruses.
  🖺 Full Text HTML: The ACE-2 receptor accelerates but is not biochemically required for SARS-CoV-2 membrane fusion.
• Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection -
  Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored. Using participants na&iumlve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry. The number of LDGs was significantly elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10+ and CD16HI subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from PPASC displayed higher NET forming ability and aggregation with platelets compared to LDGs from NP and NRS. Our data demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in individuals with PPASC may be associated with the development of long-term pulmonary sequelae.
  🖺 Full Text HTML: Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection
• Antibody avidity and multi-specificity combined to confer protection against SARS-CoV-2 and resilience against viral escape -
  SARS-CoV-2, the causative agent of COVID-19, has been responsible for a global pandemic. Monoclonal antibodies have been used as antiviral therapeutics, but have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs), and in deployment by the need for high doses. In this study, we leverage the MULTI-specific, multi-Affinity antiBODY (Multabody, MB) platform, derived from the human apoferritin protomer, to drive the multimerization of antibody fragments and generate exceptionally potent and broad SARS-CoV-2 neutralizers. CryoEM revealed a high degree of homogeneity for the core of these engineered antibody-like molecules at 2.1 [A] resolution. We demonstrate that neutralization potency improvements of the MB over corresponding IgGs translates into superior in vivo protection: in the SARS-CoV-2 mouse challenge model, comparable in vivo protection was achieved for the MB delivered at 30x lower dose compared to the corresponding IgGs. Furthermore, we show how MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding IgGs lose their ability to neutralize potently. Multiple mAb specificities could also be combined into a single MB molecule to expand the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.
  🖺 Full Text HTML: Antibody avidity and multi-specificity combined to confer protection against SARS-CoV-2 and resilience against viral escape
• Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response -
  A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.
  🖺 Full Text HTML: Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response
• [Poster] Safeguarding People against Social Media Frauds during the COVID-19 Oxygen Supply Crisis in India -
  During the second wave of the COVID-19 pandemic in India, the drastic increase in the number of COVID cases led to a positive demand shock for medical grade oxygen. However, an inadequate supply of oxygen created a huge supply-demand gap, making people resort to social media platforms in search of oxygen cylinders for their next of kin. While it alleviated problems for the masses, these desperate posts for oxygen attracted fraudsters, resulting in numerous people not getting oxygen on time. In this paper, we present research problems that arise from this crisis and argue that deep learning can be instrumental towards their solutions. Also, we propose a graph deep learning?based framework to elucidate a possible solution and incite further research in the domain.
  🖺 Full Text HTML: [Poster] Safeguarding People against Social Media Frauds during the COVID-19 Oxygen Supply Crisis in India
• Subtle cognitive impairments in memory, attention, and executive functioning in patients with post-COVID syndrome and their relationships with clinical variables and subjective complaints -

  Background and objectives. Cognitive symptoms persisting beyond three months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID syndrome (PCS) and relationships with subjective cognitive complaints and clinical variables to provide relevant information for the understanding of cognitive dysfunction and its predictors in a clinical cohort with PCS. Methods. In this cross-sectional study, we compared cognitive performance on the clinically viable Oxford Cognitive Screen-Plus between a large post-COVID cohort (n = 282) and a socio-demographically matched healthy control group (n = 52). We assessed group differences in terms of fatigue and depression as well as relationships between cognitive dysfunction and clinical and patient-reported outcomes. Results. On a group-level, patients scored significantly lower on delayed verbal memory (non-parametric effect size r = .13), attention (r = .1), and executive functioning (r=.1) than healthy controls. In each of these domains, 10-20% of patients performed more than 1.5 SD below the healthy control mean. Delayed Memory was particularly affected and a small proportion of its variance was explained by hospitalisation (beta = -.72, p < .01) and age (beta = -.03, p < .05; R2adj. = .08). Attention scores were significantly predicted by hospitalisation (beta = -.78, p < .01) and fatigue (beta = -.04, p < .05; R2adj. = .06). Discussion. PCS is associated with long-term cognitive dysfunction, particularly in delayed verbal memory, attention, and executive functioning. Deficits in delayed memory performance seem to be of particular relevance to patients9 subjective experience of impairment. Initial disease severity, current level of fatigue, and age seem to predict cognitive performance, while time since infection, depression, and pre-existing conditions do not. Longitudinal data are needed to map long-term course of cognitive dysfunction in PCS.

  🖺 Full Text HTML: Subtle cognitive impairments in memory, attention, and executive functioning in patients with post-COVID syndrome and their relationships with clinical variables and subjective complaints

From Clinical Trials

• Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell);   Biological: Inactivated COVID-19 vaccine (Vero Cell)
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   First Affiliated Hospital Bengbu Medical College
  Active, not recruiting

• COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Tri-City COVID Attitudes Study
  Sponsor:   University of Kansas Medical Center
  Recruiting

• JT001 (VV116) for the Treatment of COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: JT001;   Drug: Placebo
  Sponsors:   Shanghai Vinnerna Biosciences Co., Ltd.;   Sponsor GmbH
  Not yet recruiting

• Boost Intentions and Facilitate Action to Promote COVID-19 Booster Take-up - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Eligibility reminder;   Behavioral: Link to a narrow set of vaccine venues;   Behavioral: Link to a broad set of vaccine venues;   Behavioral: Doctors’ recommendation and value of vaccine
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Effects of Prompt to Bundle COVID-19 Booster and Flu Shot - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder to boost protection against COVID-19;   Behavioral: Flu Tag Along;   Behavioral: COVID-19 Booster & Flu Bundle
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder that facilitates action;   Behavioral: Consistency framing;   Behavioral: Information provision about the uniqueness of the bivalent booster;   Behavioral: Information provision about bivalent booster eligibility;   Behavioral: Information provision about the severity of COVID-19 symptoms
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Respiratory Muscles After Inspiratory Muscle Training After COVID-19 - Conditions:   COVID-19;   Diaphragm Injury
  Intervention:   Device: Inspiratory Muscle Training (IMT)
  Sponsors:   RWTH Aachen University;   Philipps University Marburg Medical Center
  Recruiting

• COVID-19 Simulation Education on Nursing Students - Conditions:   COVID-19 Pandemic;   Simulation of Physical Illness
  Interventions:   Behavioral: Simulation training;   Other: Control Group
  Sponsor:   Mehmet Akif Ersoy University
  Completed

• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial - Conditions:   COVID-19;   Immunodeficiency
  Interventions:   Drug: Paxlovid 5 days;   Drug: Paxlovid 10 days;   Drug: Tixagevimab and Cilgavimab
  Sponsors:   ANRS, Emerging Infectious Diseases;   University Hospital, Geneva
  Not yet recruiting

• COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions:   SARS-CoV2 Infection;   COVID-19
  Interventions:   Device: iCura COVID-19 Antigen Rapid Home Test;   Device: RT-PCR Test
  Sponsors:   MP Biomedicals, LLC;   EDP Biotech
  Completed

• COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability - Conditions:   Sars-CoV-2 Infection;   COVID-19
  Intervention:   Device: Rapid SARS-CoV-2 Antigen Test
  Sponsors:   MP Biomedicals, LLC;   EDP Biotech
  Completed

• Safety and Immunogenicity of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine - Conditions:   COVID-19;   Vaccines
  Interventions:   Biological: AdCLD-CoV19-1 OMI (Part A);   Biological: AdCLD-CoV19-1 OMI (Part B);   Other: Placebo (Part B)
  Sponsor:   Cellid Co., Ltd.
  Active, not recruiting

• Immunogenicity Evaluation of Omicron Variant-based Vaccine and a Trivalent Vaccine in Adults Against COVID-19 in Chile - Conditions:   COVID-19;   Vaccines
  Interventions:   Biological: CoronaVac®;   Biological: Omicron Vaccine;   Biological: Trivalent Vaccine
  Sponsors:   Pontificia Universidad Catolica de Chile;   Sinovac Life Sciences Co., Ltd.
  Not yet recruiting

• Safety and Dosage of a Computerized Cognitive Training Program for Cognitive Dysfunction After COVID-19 - Conditions:   Post-Acute COVID-19;   Post Acute COVID-19 Syndrome;   Cognitive Dysfunction;   Cognitive Impairment
  Intervention:   Behavioral: CCT Long COVID
  Sponsor:   Universidad Antonio de Nebrija
  Not yet recruiting

• A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5 - Condition:   COVID-19 Pandemic
  Interventions:   Biological: V-01/V-01-B5;   Biological: V-01-351/V-01-B5;   Biological: V-01
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Active, not recruiting

From PubMed

• Genome-wide Mendelian randomization and single-cell RNA sequencing analyses identify the causal effects of COVID-19 on 41 cytokines - The elevated levels of inflammatory cytokines have attracted much attention during the treatment of COVID-19 patients. The conclusions of current observational studies are often controversial in terms of the causal effects of COVID-19 on various cytokines because of the confounding factors involving underlying diseases. To resolve this problem, we conducted a Mendelian randomization analysis by integrating the GWAS data of COVID-19 and 41 cytokines. As a result, the levels of 2 cytokines were…

• A peptide array pipeline for the development of Spike-ACE2 interaction inhibitors - In humans, coronaviruses are the cause of endemic illness and have been the causative agents of more severe epidemics. Most recently, SARS-CoV-2 was the causative agent of the COVID19 pandemic. Thus, there is a high interest in developing therapeutic agents targeting various stages of the coronavirus viral life cycle to disrupt viral propagation. Besides the development of small-molecule therapeutics that target viral proteases, there is also interest molecular tools to inhibit the initial event…

• Comparison of three different COVID-19 vaccine platforms (CoronaVac, BTN162b2, and Ad5-nCoV) in individuals with and without prior COVID-19: Reactogenicity and neutralizing antibodies - Neutralizing antibodies (NAbs) can be indicators of collective immunity, vaccine efficacy, and the longevity of the humoral response. This study aimed to compare reactogenicity and NAbs generated by three different COVID-19 vaccine platforms in individuals with and without prior COVID-19. 336 individuals vaccinated (112 with CoronaVac [inactivated virus], 112 with BNT162b2 [messenger RNA], and 112 with Ad5-nCoV [non-replicating viral vector]) were included. NAbs were quantified with the cPass…

• Serial thrombin generation and exploration of alternative anticoagulants in critically ill COVID-19 patients: Observations from Maastricht Intensive Care COVID Cohort - CONCLUSION: In a sub-group of mechanically ventilated, critically ill COVID-19 patients, despite apparent adequate anti-coagulation doses evaluated by anti-Xa levels, thrombin generation potential remained high during ICU admission independent of age, sex, body mass index, APACHE II score, cardiovascular disease, and smoking status. These observations could, only partially, be explained by (anti)coagulation and thrombosis, inflammation, and multi-organ failure. Our in vitro data suggested that…

• Investigation of Embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, Spectral analysis, DFT calculations and Molecular docking studies - Embelin (2, 5-dihydroxy-3-undecyl-1,4-benzoquinone), a benzoquinone isolated from fruits of Embelia ribes has miscellaneous biological potentials including; anticancer, anti-inflammation, antibiotic, and anti-hyperglycemic activities. Also, embelin down-regulates the overexpression of inflammatory pathways like NF-kB, TACE, TNF-α, and other cytokines. Furthermore, embelin fascinated synthetic interest as a pharmacologically active compound. The present article involves the design, synthesis, DFT…

• Does Coronavirus Disease 2019 Kill More Elderly Men than Women Due to Different Hormonal Milieu - Preliminary data depicts a much greater prevalence and high case-fatality rate in advanced age males as compared to age-matched women with severe acute respiratory syndrome-coronavirus-2 infections with high morbidity, mortality, high referral, and admission to intensive care unit with severe sequelae. However, the literature search revealed both for and against studies in this context. Thus, at present, in light of the mixed studies, it cannot be established whether low testosterone levels in…

• Microwave Assisted Synthesis of 2-amino-4-chloro-pyrimidine Derivatives: Anticancer and Computational Study on Potential Inhibitory Action against COVID-19 - We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC(50) values of 89.24±1.36 µM and 89.37±1.17 µM,…

• Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition - A key step to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to prevent the entry of the virus into the host cells. The receptor-binding domains (RBDs) of spike proteins of SARS-CoV and other human coronaviruses utilize heparan sulfate proteoglycans (HSPGs) as the primary receptors for their accumulation on the cell surface and then scan for binding to the main entry receptor angiotensin-converting enzyme 2 (ACE2). SARS-CoV and SARS-CoV-2 share structurally…

• The interplay between the airway epithelium and tissue macrophages during the SARS-CoV-2 infection - The first line of antiviral immune response in the lungs is secured by the innate immunity. Several cell types take part in this process, but airway macrophages (AMs) are among the most relevant ones. The AMs can phagocyte infected cells and activate the immune response through antigen presentation and cytokine release. However, the precise role of macrophages in the course of SARS-CoV-2 infection is still largely unknown. In this study, we aimed to evaluate the role of AMs during the SARS-CoV-2…

• Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients - Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls…

• microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An in Vitro Model - microRNAs (miRs) are proposed as critical molecular targets in SARS-CoV-2 infection. Our recent in silico studies identified seven SARS-CoV-2 specific miR-like sequences, which are highly conserved with humans, including miR-1307-3p, with critical roles in COVID-19. In this current study, Vero cells were infected with SARS-CoV-2, and miR expression profiles were thereafter confirmed by qRT-PCR. miR-1307-3p was the most highly expressed miR in the infected cells; we, therefore, transiently…

• Recent advances in transition metal-catalyzed reactions of chloroquinoxalines: Applications in bioorganic chemistry - The importance of the quinoxaline framework is exemplified by its presence in the well-known drugs such as varenicline, brimonidine, quinacillin, etc. In the past few years, preparation of a variety of organic compounds containing the quinoxaline framework has been reported by several research groups. The chloroquinoxalines were successfully used as substrates in many of these synthetic approaches due to their easy availability along with the reactivity especially towards a diverse range of…

• Move and countermove: the integrated stress response in picorna- and coronavirus-infected cells - Viruses, when entering their host cells, are met by a fierce intracellular immune defense. One prominent antiviral pathway is the integrated stress response (ISR). Upon activation of the ISR - typically though not exclusively upon detection of dsRNA - translation-initiation factor eukaryotic initiation factor 2 (eIF2) becomes phosphorylated to act as an inhibitor of guanine nucleotide-exchange factor eIF2B. Thus, with the production of ternary complex blocked, a global translational arrest…

• Medications for early treatment of COVID-19 in Australia - Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication,…

• Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion - CONCLUSIONS: GMI, an FDA-approved dietary ingredient, acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 and could become a promising candidate for preventing or treating SARS-CoV-2 associated diseases.

From Patent Search