Covid-19 Sentry

Contents

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

From Preprints

• One for all - Human kidney Caki-1 cells are highly susceptible to infection with corona- and other respiratory viruses -
  Despite the vast increase in research activity in the coronavirus field over the past two years, researchers are still heavily reliant on non-human cells, for example Vero E6, highly heterogeneous or not fully differentiated cells, such as Calu-3, or not naturally susceptible cell lines overexpressing receptor ACE2 and other accessory factors, such as TMPRSS2. Complex cell models, such as primary cell-derived air-liquid interface epithelial models are highly representative of human tissues but are expensive and time-consuming to develop and maintain and have limited suitability for high-throughput analysis. In vitro investigations of host-pathogen interactions of viruses is highly reliant on suitable cell and tissue culture models and results are only as good as the model they have been validated in. Here, we show the use of a highly characterized human kidney cell line, Caki-1, for infection with three human coronaviruses: Betacoronaviruses severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and Alphacoronavirus human coronavirus 229E (hCoV-229E). Caki-1 cells show equal or superior susceptibility to all three coronaviruses when compared to other commonly used cells lines for the cultivation of the respective virus. Furthermore, we used a panel of antibodies generated against 21 SARS-CoV-2-encoded proteins to identify their location in the infected Caki-1 cells using immunocytochemistry. Most importantly, Caki-1 cells are also susceptible to two other respiratory viruses, Influenza A virus and RSV, making them an ideal model for cross-comparison of not only a broad range of coronaviruses but respiratory viruses in general.
  🖺 Full Text HTML: One for all - Human kidney Caki-1 cells are highly susceptible to infection with corona- and other respiratory viruses
• Genomic diversity of SARS-CoV-2 can be accelerated by mutations in the nsp14 gene -
  Coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), encode a proofreading exonuclease, nonstructural protein 14 (nsp14), that helps ensure replication competence at a low evolutionary rate compared with other RNA viruses. In the current pandemic, SARS-CoV-2 has accumulated diverse genomic mutations including in nsp14. Here, to clarify whether amino acid substitutions in nsp14 affect the genomic diversity and evolution of SARS-CoV-2, we searched for amino acid substitutions in nature that may interfere with nsp14 function. We found that viruses carrying a proline-to-leucine change at position 203 (P203L) have a high evolutionary rate and that a recombinant SARS-CoV-2 virus with the P203 mutation acquired more diverse genomic mutations than wild-type virus during its replication in hamsters. Our findings suggest that substitutions, such as P203L, in nsp14 may accelerate the genomic diversity of SARS-CoV-2, contributing to virus evolution during the pandemic.
  🖺 Full Text HTML: Genomic diversity of SARS-CoV-2 can be accelerated by mutations in the nsp14 gene
• Impact of sample clarification by size exclusion on virus detection and diversity in wastewater-based epidemiology -

  The use of wastewater-based epidemiology (WBE) for early detection of virus circulation and response during the SARS-CoV-2 pandemic increased interest in and use of virus concentration protocols that are quick, scalable, and efficient. One such protocol involves sample clarification by size fractionation using either low-speed centrifugation to produce a clarified supernatant or membrane filtration to produce an initial filtrate depleted of solids, eukaryotes and bacterial present in wastewater (WW), followed by concentration of virus particles by ultrafiltration of the above. While this approach has been successful in identifying viruses from WW, it assumes that majority of the viruses of interest should be present in the fraction obtained by ultrafiltration of the initial filtrate, with negligible loss of viral particles and viral diversity. We used WW samples collected in a population of ~700,000 in southwest USA between October 2019 and March 2021, targeting three non-enveloped viruses (enteroviruses [EV], canine picornaviruses [CanPV], and human adenovirus 41 [Ad41]), to evaluate whether size fractionation of WW prior to ultrafiltration leads to appreciable differences in the virus presence and diversity determined. We showed that virus presence or absence in WW samples in both portions (filter trapped solids [FTS] and filtrate) are not consistent with each other. We also found that in cases where virus was detected in both fractions, virus diversity (or types) captured either in FTS or filtrate were not consistent with each other. Hence, preferring one fraction of WW over the other can undermine the capacity of WBE to function as an early warning system and negatively impact the accurate representation of virus presence and diversity in a population.

  🖺 Full Text HTML: Impact of sample clarification by size exclusion on virus detection and diversity in wastewater-based epidemiology
• Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters -
  Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.5 is currently the dominant SARS-CoV-2 variant and substantially evades neutralizing antibodies (NAbs). Our data show that BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters.
  🖺 Full Text HTML: Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters
• Fever temperatures modulate intraprotein dynamics and enhance the binding affinity between monoclonal antibodies and the Spike protein from SARS-CoV-2 -
  Fever is a typical symptom of most infectious diseases. While prolonged fever may be clinically undesirable, mild reversible fever (< 39, 312K) can potentiate the immune responses against pathogens. Here, using molecular dynamics, we investigated the effect of febrile temperatures (38 to 40, 311K to 313K) on the immune complexes formed by the SARS-CoV-2 spike protein with two neutralizing antibodies. We found that, at mild fever temperatures (311-312K), the binding affinities of the two antibodies improve when compared to the physiological body temperature (37, 310K). Furthermore, only at 312K, antibodies exert distinct mechanical effects on the receptor binding domains of the spike protein that may hinder SARS-CoV-2 infectivity. Enhanced antibody binding affinity may thus be obtained using appropriate temperature conditions.
  🖺 Full Text HTML: Fever temperatures modulate intraprotein dynamics and enhance the binding affinity between monoclonal antibodies and the Spike protein from SARS-CoV-2
• Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus -
  During the spread of the COVID-19 pandemic, the SARS-CoV-2 coronavirus underwent mutation and recombination events that altered its genome compositional structure, thus providing an unprecedented opportunity to check an evolutionary process in real time. The mutation rate is known to be lower than expected for neutral evolution, suggesting purifying selection and convergent evolution. We begin by summarizing the compositional heterogeneity of each viral genome by computing its Sequence Compositional Complexity (SCC). To analyze the full range of SCC diversity, we select random samples of high quality coronavirus genomes covering the full span of the pandemic. We then search for evolutionary trends that could inform us on the adaptive process of the virus to its human host by computing the phylogenetic ridge regression of SCC against time (i.e., the collection date of each viral isolate). In early samples, we find no statistical support for any trend in SCC values, although the viral genome appears to evolve faster than Brownian Motion (BM) expectation. However, in samples taken after the emergence of high fitness variants, and despite the brief time span elapsed, a driven decreasing trend for SCC and an increasing one for its absolute evolutionary rate are detected, pointing to a role for purifying selection in the evolution of SCC in the coronavirus. The higher fitness of variant genomes leads to adaptive trends of SCC over pandemic time in the coronavirus.
  🖺 Full Text HTML: Adaptive trends of sequence compositional complexity over pandemic time in the SARS-CoV-2 coronavirus
• NC-COVID: A Time-Varying Compartmental Model for Estimating SARS-CoV-2 Infection Dynamics in North Carolina, US -

  Efforts to track and model SARS-CoV-2 infection dynamics in the population have been complicated by certain aspects of the transmission characteristics, which include a pre-symptomatic infectious phase as well as asymptomatic infectious individuals. Another problem is that many models focus on case count, as there there has been (and is) limited data regarding infection status of members of the population, which is the most important aspect for constructing transmission models. This paper describes and explain the parameterization, calibration, and revision of the NC-COVID model, a compartmental model to estimate SARS-CoV-2 infection dynamics for the state of North Carolina, US. The model was developed early in the pandemic to provide rapid, up-to-date state-level estimates of the number of people who were currently infected, were immune from a prior infection, and remained susceptible to infection. As a post modeling exercise, we assessed the veracity of the model by comparing its output to SARS-CoV-2 viral particle concentrations detected in wastewater data and to estimates of people infected using COVID-19 deaths. The NC-COVID model was highly correlated with these independently derived estimates, suggesting that it produced accurate estimates of SARS-CoV-2 infection dynamics in North Carolina.

  🖺 Full Text HTML: NC-COVID: A Time-Varying Compartmental Model for Estimating SARS-CoV-2 Infection Dynamics in North Carolina, US
• Development of criteria for cognitive dysfunction in post-COVID syndrome: the IC-CoDi-COVID approach -

  Background. We aimed to develop objective criteria for cognitive dysfunction associated with the post-COVID syndrome. Methods. Four hundred and four patients with post-COVID syndrome from two centers were evaluated with comprehensive neuropsychological batteries. The International Classification for Cognitive Disorders in Epilepsy (IC-CoDE) framework was adapted and implemented. A complementary data-driven approach based on unsupervised machine-learning clustering algorithms was also used to evaluate the optimal classification and cutoff points. Results. According to the developed criteria, 41.2% and 17.3% of the sample were classified as having at least one cognitive domain impaired using -1 and -1.5 standard deviations as cutoff points. Attention/processing speed was the most frequently impaired domain. There were no differences in base rates of cognitive impairment between the two centers. Clustering analysis revealed two clusters according to the severity of cognitive impairment, but there was no difference in cognitive profiles. Cognitive impairment was associated with younger age and lower education levels, but not hospitalization. Conclusions. We propose a harmonization of the criteria to define and classify cognitive impairment in the post-COVID syndrome. These criteria may be extrapolated to other neuropsychological batteries and settings, contributing to the diagnosis of cognitive deficits after COVID-19 and facilitating multicenter studies to guide biomarker investigation and therapies.

  🖺 Full Text HTML: Development of criteria for cognitive dysfunction in post-COVID syndrome: the IC-CoDi-COVID approach
• Impact of vaccination on the presence and severity of symptoms of hospitalised patients with an infection by the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1). -

  Objectives: The emergence of SARS-CoV-2 variants raised questions over the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalised patients. Methods: We conducted an international, multicentric, retrospective study in 14 centres (Bulgaria, Croatia, France, Turkey). We collected data on patients hospitalised ≥24 hours between 01/12/2021 and 03/03/2022, with PCR-confirmed infection at a time of exclusive Omicron circulation, with hospitalisation related or not to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least 2 injections of either mRNA and/or ChAdOx1-S, or 1 injection of Ad26.CoV2-S vaccines. Results: Among the 1215 patients (median [IQR] age 73.0 [57.0; 84.0]; 51.3% males), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (RR=0.50 [0.32-0.77]), ICU admission (R=0.40 [0.26-0.62], and oxygen requirement (RR=0.34 [0.25-0.46]), independently of age and comorbidities. When co-analysing these Omicron patients with 948 Delta patients from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (RR=0.53 [0.37-0.76]), ICU admission (R=0.19 [0.12-0.28], and oxygen requirements (RR=0.50 [0.38-0.67]), independently of age, comorbidities and vaccination status. Conclusions: mRNA- and adenovirus-based vaccines have remained effective on severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independently of vaccination and patient characteristics.

  🖺 Full Text HTML: Impact of vaccination on the presence and severity of symptoms of hospitalised patients with an infection by the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1).
• Rare predicted loss-of-function variants of type I IFN immunity genes are associated with critical COVID-19 -

  Background We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and autoantibodies against type I IFN in another 15-20% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI:1.5-528.7, P=1.1x10-4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P=2.1x10-4). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P=3.4x10-3). When these 14 loci and TLR7 were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P=4.7x10-7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P=0.02). Finally, the patients 13 with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10-5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie lifethreatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

  🖺 Full Text HTML: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with critical COVID-19
• COVID-19 vaccine equity and the right to health for displaced Venezuelans in Latin America -

  Given the magnitude of Venezuelan displacement in Latin America, there is a need to assess how migrants were, and will continue to be, addressed in COVID-19 vaccination policies. To explore migration status as a dimension of vaccine equity in Latin America and in relation to international human rights, we assessed national vaccination plans, peer-reviewed, and gray literature published between January 2020 and June 2021. Three key rights-related concerns were found to restrict the health rights of migrants in the region: 1) lack of prioritization of migrants in vaccine distribution; 2) onerous documentation requirements to be eligible for COVID-19 vaccination; and (3) how pervasive anti-migrant discrimination limited equitable health care access. While international human rights law prohibits against discrimination based on migration status, few countries analyzed realized their obligations to provide equal access to COVID-19 vaccines to non-citizens, including displaced Venezuelans. Especially for migrants and displaced people, effective and sustainable vaccination strategies for COVID-19 and future pandemics in Latin America must be guided not only by epidemiological risk but also seek to align with human rights obligations. To achieve this, States must also take special measures to facilitate vaccine access for communities facing systemic discrimination, exclusion, and marginalization.

  🖺 Full Text HTML: COVID-19 vaccine equity and the right to health for displaced Venezuelans in Latin America
• A Systematic Review on Medical Oxygen Ecosystem: Current State and Recent Advancements -

  Background: Medical-grade oxygen is an essential component of modern healthcare, with a wide variety of applications ranging from supplemental use in surgery and trauma patients to the primary medication in oxygen therapy. This is the most effective treatment for any respiratory illness. Despite the importance of medicinal oxygen for public health and its demand as a life-saving drug, research on the subject is limited, with the majority of studies conducted following the outbreak of the COVID-19 pandemic. Due to the lack of empirical studies, we aimed to compile the recent research efforts with the current state of the field to guide the new researchers around the topic. Methods: We have performed a systematic review targeting the medical oxygen ecosystem, following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). For the study, we have limited our scope to healthcare facilities and domiciliary applications of medical oxygen and considered the articles published in the last thirty years. Results: Our systematic search resulted in forty-three scientific articles, with three more miscellaneous articles appended for painting a complete picture. Based on the selected articles, the complete oxygen ecosystem was categorized into five main fields. Conclusion: We have presented an in-depth analysis of the research works found through the systematic search, and a brief discussion on the current scenario of the subject referencing these studies. We hope to benefit researchers approaching this area through this study, and guide them around the topic.

  🖺 Full Text HTML: A Systematic Review on Medical Oxygen Ecosystem: Current State and Recent Advancements
• A SEIRD+V Model for the Effect of Vaccination and Social Distancing on SARS-CoV-2 Infection and Mortality -

  We present a deterministic, calibrated Susceptible-Exposed-Infected-Recovered-Dead + Vaccinated (SEIRD+V) model that simulates the spread and containment of COVID-19. We use the model to compare the effectiveness of vaccination vs. social distancing on death prevention and total and peak infection reduction. We find that vaccination drastically reduces total deaths from COVID-19, as well as total and peak infections with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We find that social distancing plays a role in reducing total COVID-19 deaths, but its impact is less pronounced when vaccine efficacy and vaccination fraction are both high. Social distancing also plays a role in reducing total and peak infections, which is attenuated in the presence of vaccination. We employed a thresholding methodology to assess the requirements of vaccine efficacy and the vaccination fraction to limit total COVID-19 deaths and peak infections to a 5% threshold. Our thresholding results quantify the impact of social distancing on total COVID-19 deaths and peak infections and are significant in their ability to inform public health policy for future outbreaks, as well as for SARS-CoV-2 itself as it continues to mutate and alter its transmissibility.

  🖺 Full Text HTML: A SEIRD+V Model for the Effect of Vaccination and Social Distancing on SARS-CoV-2 Infection and Mortality
• Scoping review and meta-analysis of COVID-19 epidemiological parameters for modeling from early Asian studies -

  Retrospective epidemiological models are powerful tools to understand its transmission dynamics and to assess the efficacy of different control measures. This study summarises key epidemiological parameters of COVID-19 for retrospective mathematical and clinical modeling. A review of scientific papers and preprints published in English between 1 January and 15 April 2020 in PubMed, MedRxiv and BioRxiv was performed to obtain epidemiological parameters of the initial stage of COVID-19 pandemic in Asia. After excluding articles with unacceptable risks of bias and those that remained as preprints as of 15 November 2021, meta-analyses were performed to derive summary effect estimates from the data collected using the statistical software R. Out of 4,893 articles identified, 88 provided data for 22 parameters for the overall population and 7 specifically for children. Meta-analyses were conducted considering time period as a categorical moderator when it was statistically significant. The results obtained are essential for building more reliable models to help clinicians and policymakers improve their knowledge on COVID-19 and apply it in future decisions.

  🖺 Full Text HTML: Scoping review and meta-analysis of COVID-19 epidemiological parameters for modeling from early Asian studies
• 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

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

• 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

• Exploratory Clinical Study to Evaluation of the Safety and Immunogenicity of Bivalent Vaccine V-01D-351 - Condition:   COVID-19 Pandemic
  Interventions:   Biological: V-01D-351;   Biological: CoronaVac
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Active, not recruiting

• 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

From PubMed

• Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial - BACKGROUND: Well tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes.

• Synthesis of bee venom loaded chitosan nanoparticles for anti-MERS-COV and multi-drug resistance bacteria - This study aims to fully exploit the natural compound; bee venom (BV) as a substance that can kill and inhibit the growth of microbes and viruses. For this target, BV was loaded onto a safe, natural, and economically inexpensive polymer, which is chitosan (Ch) in its nano-size form using the ionic gelation method and chemical crosslinking agent (sodium tripolyphosphate; TPP). The findings illustrated that chitosan nanoparticles (ChNPs) were prepared thru this method exhibited spherical shape and…

• Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication - Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein…

• 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…

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