Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
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From Preprints

• Alternative cell entry mechanisms for SARS-CoV-2 and multiple animal viruses -
  The cell entry mechanism of SARS-CoV-2, the causative agent of the COVID-19 pandemic, is not fully understood. Most animal viruses hijack cellular endocytic pathways as an entry route into the cell. Here, we show that in cells that do not express serine proteases such as TMPRSS2, genetic depletion of all dynamin isoforms blocked the uptake and strongly reduced infection with SARS-CoV-2 and its variant Delta. However, increasing the viral loads partially and dose-dependently restored infection via a thus far uncharacterized entry mechanism. Ultrastructural analysis by electron microscopy showed that this dynamin-independent endocytic processes appeared as 150-200 nm non-coated invaginations and was efficiently used by numerous mammalian viruses, including alphaviruses, influenza, vesicular stomatitis, bunya, adeno, vaccinia, and rhinovirus. Both the dynamin-dependent and dynamin-independent infection of SARS-CoV-2 required a functional actin cytoskeleton. In contrast, the alphavirus Semliki Forest virus, which is smaller in diameter, required actin only for the dynamin-independent entry. The presence of TMPRSS2 protease rescued SARS-CoV-2 infection in the absence of dynamins. Collectively, these results indicate that some viruses such as canine parvovirus and SARS-CoV-2 mainly rely on dynamin for endocytosis-dependent infection, while other viruses can efficiently bypass this requirement harnessing an alternative infection entry route dependent on actin.
  🖺 Full Text HTML: Alternative cell entry mechanisms for SARS-CoV-2 and multiple animal viruses
• Lack of detection of SARS-CoV-2 in Wildlife from Kerala, India in 2020-21 -
  Spill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), 6 Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus (Common Palm Civet), 5 Viverricula indica (Small Indian Civet), 4 Herpestes edwardsii (Common Mongoose), 10 Panthera tigris (Bengal Tiger), 8 Panthera pardus fusca (Indian Leopard), 4 Prionailurus bengalensis (Leopard cats), 2 Felis chaus (Jungle cats), 2 Cuon alpinus (Wild dogs), and 1 Melursus ursinus (sloth bear).
  🖺 Full Text HTML: Lack of detection of SARS-CoV-2 in Wildlife from Kerala, India in 2020-21
• Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants -
  SARS-CoV-2 has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of eight SARS-CoV-2 variants. Their sera were titrated against 14 SARS-CoV-2 variants and the resulting titers visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant), and a considerably more distributed positioning among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/5, the BA.5 descendants BF.7 and BQ.1.18; the BA.2.75 descendant BN.1.3.1; and the BA.2-derived recombinant XBB.2). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. The results highlight the potential of using variant-specifically infected hamster sera for the continued antigenic characterisation of SARS-CoV-2.
  🖺 Full Text HTML: Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants
• Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub -

  Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

  🖺 Full Text HTML: Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub
• Projecting COVID-19 intensive care admissions in the Netherlands for policy advice: February 2020 to January 2021 -

  Introduction: Model projections of COVID-19 incidence into the future help policy makers about decisions to implement or lift control measures. During 2020, policy makers in the Netherlands were informed on a weekly basis with short-term projections of COVID-19 intensive care unit (ICU) admissions. Here we present the model and the procedure by which it was updated. Methods: the projections were produced using an age-structured transmission model. A consistent, incremental update procedure that integrated all new surveillance and hospital data was conducted weekly. First, up-to-date estimates for most parameter values were obtained through re-analysis of all data sources. Then, estimates were made for changes in the age-specific contact rates in response to policy changes. Finally, a piecewise constant transmission rate was estimated by fitting the model to reported daily ICU admissions, with a change point analysis guided by Akaike9s Information Criterion. Results: The model and update procedure allowed us to make mostly accurate weekly projections, accounting for recent and future policy changes, and to adapt the estimated effectiveness of the policy changes based only on the natural accumulation of incoming data. Discussion: The model incorporates basic epidemiological principles and most model parameters were estimated per data source. Therefore, it had potential to be adapted to a more complex epidemiological situation, as it would develop after 2020.

  🖺 Full Text HTML: Projecting COVID-19 intensive care admissions in the Netherlands for policy advice: February 2020 to January 2021
• A new Omicron lineage with Spike Y451H mutation that dominated a new COVID-19 wave in Kilifi, Coastal Kenya: March-May 2023 -

  We report a newly emerged SARS-CoV-2 Omicron lineage, named FY.4, that has two unique mutations; spike:Y451H and ORF3a:P42L. FY.4 emergence has coincided with increased SARS-CoV-2 cases in coastal Kenya, April-May 2023. We demonstrate the value of continued SARS-CoV-2 genomic surveillance in the post-acute pandemic era in understanding new COVID-19 outbreaks.

  🖺 Full Text HTML: A new Omicron lineage with Spike Y451H mutation that dominated a new COVID-19 wave in Kilifi, Coastal Kenya: March-May 2023
• Integration of human organoids single-cell transcriptomic profiles and human genetics repurposes critical cell type-specific drug targets for severe COVID-19 -

  Human organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. Advances in single-cell RNA sequencing (scRNA-seq) technology and genome-wide association study (GWAS) have accelerated the biological and therapeutic interpretation of trait-relevant cell types or states. Here, we constructed a computational framework to integrate atlas-level organoid scRNA-seq data, GWAS summary statistics, expression quantitative trait loci, and gene-drug interaction data for distinguishing critical cell populations and drug targets relevant to COVID-19 severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID-19 outcomes. Notably, subset of lung mesenchymal stem cells (MSCs) increased proximity with fibroblasts predisposed to repair COVID-19-damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID-19, and this cell subset showed a notable increase in cell-to-cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID-19 in a cell-type-specific manner. Overall, our results showcase that host genetic determinants have cellular specific contribution to COVID-19 severity, and identification of cell type-specific drug targets may facilitate to develop effective therapeutics for treating severe COVID-19 and its complications.

  🖺 Full Text HTML: Integration of human organoids single-cell transcriptomic profiles and human genetics repurposes critical cell type-specific drug targets for severe COVID-19
• Inclusion Criteria for Extracorporeal Membrane Oxygenation (ECMO) in Patients with Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: A Systematic Review -

  Introduction: At the end of 2019, in the city of Wuhan, China, a virus of the family of coronaviruses first appeared, mainly affecting the respiratory system, which was called SARS-COV-2 and causes COVID-19. Although in most patients, it occurs with mild symptomatology, however, a significant percentage (15-30%) will develop acute respiratory distress syndrome (ARDS) with increased chances of intubation and mechanical ventilation. In special cases of severe disease, where the oxygenation of the patient is not improved by the use of the ventilator, extracorporeal membrane oxygenation (ECMO) can be applied, a technique that has been used in previous pandemics that affected the respiratory system. Aim: To investigate the evidence of the appliance of the ECMO, based on international literature, of the extracorporeal membrane oxygenator in patients with severe respiratory failure due to Covid-19 disease. Method: Articles were searched on the international bases of scientific studies PubMed, Cochrane Library, and Google Scholar. This review was carried out using meta-analysis and international guidelines. Results: Four articles were included where there was an agreement on the basic characteristics of patients, which can be considered as selection criteria. The primary criteria indicate the age, where the patient must be under 65 years old, and the body mass index (BMI) should be below 40. In addition, it is very important that there is no serious underlying pathology such as multi-organ failure syndrome. Also, the mechanical ventilation should not exceed seven (7) days until the placement of the ECMO, while all the other therapeutic methods, such as the prone position, neuromuscular blockers, and the appropriate positive end-expiratory pressure of the airways (Positive end-expiratory pressure - PEEP) should be already applied. Conclusions: The application of ECMO is widely used as a treatment for patients with severe COVID-19 disease. However, in order to have the best therapeutic results while reducing hospitalization costs, it is necessary to follow the guidelines regarding the selection of patients who will benefit substantially. Key Words: ECMO, ECMO criteria, ECMO guidelines, ARDS, Covid-19 treatment, ICU

  🖺 Full Text HTML: Inclusion Criteria for Extracorporeal Membrane Oxygenation (ECMO) in Patients with Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: A Systematic Review
• The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022 -
  The COVID-19 pandemic changed the way people lived, worked, and studied around the world, with direct consequences for domestic energy use. This study assesses the impact of COVID-19 lockdowns in the first two years of the pandemic on household electricity and gas use in England and Wales. Using data for 508 (electricity) and 326 (gas) homes, elastic net regression, neural network and extreme gradient boosting predictive models were trained and tested on pre-pandemic data. The most accurate model for each household was used to create counterfactuals (predictions in the absence of COVID-19) against which observed pandemic energy use was compared. Median monthly model error (CV(RMSE)) was 3.86% (electricity) and 3.19% (gas) and bias (NMBE) was 0.21% (electricity) and -0.10% (gas). Our analysis showed that on average (electricity; gas) consumption increased by (7.8%; 5.7%) in year 1 of the pandemic and by (2.2%; 0.2%) in year 2. The greatest increases were in the winter lockdown (January – March 2021) by 11.6% and 9.0% for electricity and gas, respectively. At the start of 2022 electricity use remained 2.0% higher while gas use was around 1.9% lower than predicted. Households with children showed the greatest increase in electricity consumption during lockdowns, followed by those with adults in work. Wealthier households increased their electricity consumption by more than the less wealthy and continued to use more than predicted throughout the two-year period while the less wealthy returned to pre-pandemic or lower consumption from summer 2021. Low dwelling efficiency was associated with a greater increase in energy consumption during the pandemic. Additionally, this study shows the value of different machine learning techniques for counterfactual modelling at the individual-dwelling level, and our approach can be used to robustly estimate the impact of other events and interventions.
  🖺 Full Text HTML: The impact of COVID-19 on household energy consumption in England and Wales from April 2020 – March 2022
• “Lessons from the COVID War”: An incomplete analysis of U.S. COVID-19 policies -
  A new book, “Lessons from the COVID War”, attempts to analyze reasons for the failure to contain the SARS-CoV-2 virus in the United States. Based primarily on interviews with government officials and advisors, it neglects the quantitative studies of virus spread and containment associated with testing, tracing, and quarantine. More successful policies of several countries that had a fraction of the U.S. COVID-19 death rate are ignored.
  🖺 Full Text HTML: “Lessons from the COVID War”: An incomplete analysis of U.S. COVID-19 policies
• RNA structure and multiple weak interactions balance the interplay between RNA binding and phase separation of SARS-CoV-2 nucleocapsid -
  The nucleocapsid (N) protein of SARS-CoV-2 binds viral RNA, condensing it inside the virion, and phase separating with RNA to form liquid-liquid condensates. There is little consensus on what differentiates sequence-independent N-RNA interactions in the virion or in liquid droplets from those with specific genomic RNA motifs necessary for viral function inside infected cells. To identify the RNA structures and the N domains responsible for specific interactions and phase separation, we use the first 1000nt of viral RNA and short RNA segments designed as models for single-stranded and paired RNA. Binding affinities estimated from fluorescence anisotropy of these RNAs to the two folded domains of N (the NTD and CTD) and comparison to full-length N demonstrate that the NTD binds preferentially to single-stranded RNA, and while it is the primary RNA binding site, it is not essential to phase separation. Nuclear magnetic resonance spectroscopy identifies two RNA binding sites on the NTD: a previously characterized site and an additional although weaker RNA-binding face that becomes prominent when binding to the primary site is weak, such as with dsRNA or a binding-impaired mutant. Phase separation assays of nucleocapsid domains with different RNA structures support a model where multiple weak interactions, such as with the CTD or the NTD's secondary face promote phase separation, while strong, specific interactions do not. These studies indicate that both strong and multivalent weak N-RNA interactions underlie the multifunctional abilities of N.
  🖺 Full Text HTML: RNA structure and multiple weak interactions balance the interplay between RNA binding and phase separation of SARS-CoV-2 nucleocapsid
• Prothrombotic factors associated with COVID-19 complications: A systematic review preprint. -
  BACKGROUND: The COVID-19 pandemic caused deaths and severe clinical complications associated with thrombosis and hypercoagulability, motivating this literature review. OBJECTIVE: To analyze the scope of scientific publications that demonstrate an association of thromboembolism with complications of COVID-19. METHOD: A systematic literature review was performed to identify clinical complications associated with thrombosis in people exposed to SARS-CoV-2 infection. The articles were selected from MEDLINE database after being screened and filtered to extract the methodologies used and the evidence of clinical complications by compromised organs or systems and pathology description. The evidence was extracted in Cohort Studies for statistical analysis and hypothesis testing (t-test). RESULTS: A total of 208 studies were selected. Observational Studies were predominant, corresponding to 64% of the total, and other methodologies corresponded to 9% in the inclusion. Review articles were excluded and corresponded to the remaining 27% of the selected articles. Subsequently, 150 articles were screened, and 121 were filtered. Among these, 11 Cohort Studies were extracted as the sample, which were eligible for analysis and subsequent Hypothesis Test. This test showed a Mean Difference of 4.74 [Ha (μ=8.08 Exposure) > (μ=3.33 No exposure)], with a p-value of 0.096 for a 95% confidence interval. Despite the numerical value of the difference in the means due to the influence of variance, the test result was not statistically significant due to the small number of the sample of Cohort studies. CONCLUSION: It was observed that prothrombotic conditions were present and translated by hypercoagulability in the evaluated articles. Individuals exposed to SARS-CoV-2 infection have been shown to experience complications caused by thrombosis more often than the unexposed. It is suggested to conduct a Meta-analysis with a larger sample of Cohort Studies to further analyze this association.
  🖺 Full Text HTML: Prothrombotic factors associated with COVID-19 complications: A systematic review preprint.
• Knowledge graphs and wikidata subsetting -
  Knowledge graphs have successfully been adopted by academia, governement and industry to represent large scale knowledge bases. Open and collaborative knowledge graphs such as Wikidata capture knowledge from different domains and harmonize them under a common format, making it easier for researchers to access the data while also supporting Open Science. Wikidata keeps getting bigger and better, which subsumes integration use cases. Having a large amount of data such as the one presented in a scopeless Wikidata offers some advantages, e.g., unique access point and common format, but also poses some challenges, e.g., performance. Regular wikidata users are not unfamiliar with running into frequent timeouts of submitted queries. Due to its popularity, limits have been imposed to allow for fair access to many. However this suppreses many interesting and complex queries that require more computational power and resources. Replicating Wikidata on one’s own infrastructure can be a solution which also offers a snapshot of the contents of wikidata at some given point in time. There is no need to replicate Wikidata in full, it is possible to work with subsets targeting, for instance, a particular domain. Creating those subsets has emerged as an alternative to reduce the amount and spectrum of data offered by Wikidata. Less data makes more complex queries possible while still keeping the compatibility with the whole Wikidata as the model is kept. In this paper we report the tasks done as part of a Wikidata subsetting project during the Virtual BioHackathon Europe 2020 and SWAT4(HC)LS 2021, which had already started at NBDC/DBCLS BioHackathon 2019 in Japan, SWAT4(HC)LS hackathon 2019, and Virtual COVID-19 BioHackathon 2019. We describe some of approaches we identified to create subsets and some susbsets from the Life Sciences domain as well as other use cases we also discussed.
  🖺 Full Text HTML: Knowledge graphs and wikidata subsetting
• Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic -
  The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors’ recruitment and retention during 2020 with respect to the 2017-2019 period, considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented improvement in performances.
  🖺 Full Text HTML: Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic
• COVID-related anthropause highlights the impact of marine traffic on breeding little penguins -
  The COVID-19 pandemic and its lock-down measures have resulted in periods of reduced human activity, known as anthropause. While this period was expected to be favorable for the marine ecosystem, due to a probable reduction of pollution, shipping traffic, industrial activity and fishing pressure, negative counterparts such as the increased use of disposable plastic and reduced fisheries surveillance and enforcement could counterbalance these positive effects. Simultaneously, on-land pressure due to human disturbance and tourism should have drastically decreased, potentially benefiting land-based marine breeders such as seabirds. Thus, long-term datasets became crucial to differentiate between historical trends and any evident changes resulting from the anthropause. We analyzed 11 years of data on several biological parameters of little penguins (Eudyptula minor) from the Penguin Parade (R), a popular tourist attraction at Phillip Island, Australia. We investigated the impact of anthropogenic activities on penguin behavior during the breeding season measured by (1) distribution at sea, (2) colony attendance, (3) isotopic niche (4) chick meal mass, and (5) offspring investment against shipping traffic and number of tourists. The 2020 lock-downs resulted in a near absence of tourists visiting the Penguin Parade (R), which was otherwise visited by 800,000+ visitors on average per year. However, our long-term analysis showed no effect of the presence of visitors on little penguins' activities. Surprisingly, the anthropause did not triggered any changes in maritime traffic intensity and distribution in the region. While we found significant inter- and intra-annual variations for most parameters, we detected a negative effect of marine traffic on the foraging efficiency. Our results suggest that environmental variations have a greater influence on the breeding behavior of little penguins compared to short-term anthropause events. Our long-term dataset was key to test whether changes in anthropogenic activities affected the wildlife during the COVID-19 pandemic.
  🖺 Full Text HTML: COVID-related anthropause highlights the impact of marine traffic on breeding little penguins

From Clinical Trials

• Probiotic and Colchicine in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Colchicine 0.5 MG;   Dietary Supplement: Probiotic Formula;   Other: Standard protocol
  Sponsor:   Ain Shams University
  Completed

• COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists - Condition:   COVID-19
  Interventions:   Behavioral: Standard implementation webinar and online training;   Behavioral: Virtual facilitation
  Sponsors:   University of North Carolina, Chapel Hill;   University of Arkansas;   University of South Carolina;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C);   Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition:   COVID-19
  Interventions:   Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell);   Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell);   Biological: control group;   Biological: Placebo group
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients - Conditions:   COVID-19;   Hospitalized COVID-19 Patients
  Interventions:   Drug: Lopinavir / Ritonavir;   Drug: Remdesivir (RDV);   Drug: Tocilizumab;   Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
  Sponsors:   Lebanese University;   Hospital Saydet Zgharta University Medical Center
  Recruiting

• Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy - Condition:   Post-COVID-19 Syndrome
  Interventions:   Other: sensory re-education training;   Other: traditional treatment
  Sponsor:   Cairo University
  Not yet recruiting

• Comprehensive Imaging Exam of Convalesced COVID-19 Patients - Conditions:   COVID-19;   COVID Long-Haul
  Interventions:   Other: Magnetic Resonance Imaging;   Other: Ultra-High Resolution Computed Tomography (CT) Scan
  Sponsors:   Johns Hopkins University;   Canon Medical Systems, USA
  Enrolling by invitation

• UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study) - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults - Condition:   COVID-19
  Interventions:   Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection;   Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection
  Sponsor:   Clover Biopharmaceuticals AUS Pty Ltd
  Not yet recruiting

• The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002 - Condition:   COVID-19
  Interventions:   Biological: LYB002V14;   Biological: LYB002V14A;   Biological: LYB002CA
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• Evaluate the Safety and Immunogenicity of Different Booster Dose Levels of Monovalent and Bivalent SARS-CoV-2 rS Vaccines in Adults ≥ 50 Years - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2540 (5, 10, 25 μg);   Biological: NVX-CoV2373 (5 μg);   Biological: Bivalent BA.4/5 Omicron subvariant
  Sponsor:   Novavax
  Not yet recruiting

• Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection. - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Drug: Remdesivir
  Sponsors:   University of Derby;   University of Exeter;   Peninsula Clinical Trials Unit;   University Hospitals of Derby and Burton NHS Foundation Trust
  Not yet recruiting

• The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001 - Conditions:   COVID-19;   Vaccine Reaction
  Interventions:   Biological: LYB001;   Biological: CoronaVac
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• SAFETY AND EFFICACY OF ANAKINRA TREATMENT FOR PATIENTS WITH POST ACUTE COVID SYNDROME - Condition:   Post-Acute COVID-19 Syndrome
  Interventions:   Drug: Placebo;   Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Not yet recruiting

• The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19 - Conditions:   Coronavirus Disease;   COVID-19;   Long Covid-19;   Telerehabilitation
  Interventions:   Device: KNEESUP smart knee assistive device + KNEESUP care APP;   Device: KNEESUP care APP;   Behavioral: Healthy consulation
  Sponsor:   Shang-Lin Chiang
  Recruiting

From PubMed

• Cell surface nucleocapsid protein expression: A betacoronavirus immunomodulatory strategy - We recently reported that SARS-CoV-2 nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the common cold human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and noninfected cells by binding heparan…

• AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor - Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays and…

• A single polymorphic residue in humans underlies species-specific restriction of HSV-1 by the antiviral protein MxB - Myxovirus resistance proteins (MxA and MxB) are interferon-induced proteins that exert antiviral activity against a diverse range of RNA and DNA viruses. In primates, MxA has been shown to inhibit myxoviruses, bunyaviruses, and hepatitis B virus, whereas MxB restricts retroviruses and herpesviruses. As a result of their conflicts with viruses, both genes have been undergoing diversifying selection during primate evolution. Here, we investigate how MxB evolution in primates has affected its…

• PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell and tissue specific manner - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD ^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon, indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…

• IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition - The glycosylation of IgG plays a critical role during human SARS-CoV-2, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during acute viral infection in humans. In vitro evidence suggests that the glycosylation of IgM inhibits T cell proliferation and alters complement activation rates. The analysis of IgM N-glycosylation from healthy controls and hospitalized COVID-19 patients reveals that mannosylation and sialyation levels…

• Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes - In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents-during the pandemic, the prevalence of obesity increased by ∼37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced…

• Universal features of Nsp1-mediated translational shutdown by coronaviruses - Nonstructural protein 1 (Nsp1) produced by coronaviruses shuts down host protein synthesis in infected cells. The C-terminal domain of SARS-CoV-2 Nsp1 was shown to bind to the small ribosomal subunit to inhibit translation, but it is not clear whether this mechanism is broadly used by coronaviruses, whether the N-terminal domain of Nsp1 binds the ribosome, or how Nsp1 specifically permits translation of viral mRNAs. Here, we investigated Nsp1 from three representative Betacoronaviruses -…

• Saline nasal irrigation and gargling in COVID-19: a multidisciplinary review of effects on viral load, mucosal dynamics, and patient outcomes - With unrelenting SARS-CoV-2 variants, additional COVID-19 mitigation strategies are needed. Oral and nasal saline irrigation (SI) is a traditional approach for respiratory infections/diseases. As a multidisciplinary network with expertise/experience with saline, we conducted a narrative review to examine mechanisms of action and clinical outcomes associated with nasal SI, gargling, spray, or nebulization in COVID-19. SI was found to reduce SARS-CoV-2 nasopharyngeal loads and hasten viral…

• Design, Synthesis and Structure-Activity Relationship Studies of Protein Kinase CK2 Inhibitors Containing a Purine Scaffold - Protein kinase CK2 (CK2) is involved in the suppression of gene expression, protein synthesis, cell proliferation, and apoptosis, thus making it a target protein for the development of therapeutics toward cancer, nephritis, and coronavirus disease 2019. Using the solvent dipole ordering-based method for virtual screening, we identified and designed new candidate CK2α inhibitors containing purine scaffolds. Virtual docking experiments supported by experimental structure-activity relationship…

• A fish perspective on SARS-CoV-2: toxicity of benzalkonium chloride on Danio rerio - SARS-CoV-2 outbreak lead to an increased marketing of disinfectants, creating a potential environmental problem. For instance, pre-pandemic environmental levels of the disinfectant benzalkonium chloride (BAC) ranging from 0.5 to 5 mgL^(-1) in effluents were expected to further increase threatening aquatic life. Our aim was to characterize potential adverse effects after an acute exposure of zebrafish to different concentrations of BAC. An increase in the overall swimming activity, thigmotaxis…

• Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein - Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan interactions. We hypothesize that polyvalent nano-lectins with flexibly linked…

• Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-β - Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19…

• Anti-Inflammatory Effects of Dexamethasone in COVID-19 Patients: Translational Population PK/PD Modeling and Simulation - Dexamethasone (DEX) given at a dose of 6 mg once-daily for 10 days is a recommended dosing regimen in patients with COVID-19 requiring oxygen therapy. We developed a population pharmacokinetic and pharmacodynamic (popPK/PD) model of DEX anti-inflammatory effects in COVID-19 and provide simulations comparing the expected efficacy of four dosing regimens of DEX. Nonlinear mixed-effects modeling and simulations were performed using Monolix Suite version 2021R1 (Lixoft, France). Published data for…

• The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2 - The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (Momordica charantia), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC50 ~ 0.2 μM) with…

• Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease - The SARS-CoV-2 main protease (M^(pro)) plays an essential role in the coronavirus lifecycle by catalyzing hydrolysis of the viral polyproteins at specific sites. M^(pro) is the target of drugs, such as nirmatrelvir, though resistant mutants have emerged that threaten drug efficacy. Despite its importance, questions remain on the mechanism of how M^(pro) binds its substrates. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to evaluate structural and dynamical…

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