Covid-19 Sentry

Contents

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

From Preprints

• Rehabilitation in Survivors of COVID-19 (RE2SCUE): a nonrandomized, controlled, and open protocol -

  Objective: This study aimed to evaluate the effects of physical rehabilitation for adults with sequelae after COVID-19. Methods: This clinical, nonrandomized, controlled, and open study will examine 82 participants who have met the inclusion criteria and who will be divided into treatment and control groups according to participant preference. The intervention group will receive face-to-face care; the control group will receive remote educational guidance for 8 weeks, with pre-post evaluations. The primary outcomes are dyspnea, fatigue, and exercise capacity; the secondary outcomes are lung function, heart rate variability, handgrip strength, knee extensor strength and electrical activity, physical activity, functional limitation, cognitive function, depression and anxiety, and biochemical measures of hypoxia, inflammation, oxidative stress, blood glucose, and lactate blood tests. The survey will follow the Standard Protocol Items for Randomized Trials guidelines, and the results will be reported according to the Consolidated Standards of Reporting Trials guidelines. Effects will be assessed based on the intent-to-treat data collected. Analysis of covariance will be used for the initial and final evaluations, with a significance level of 5%. Results and Conclusions: The results will show the effectiveness of rehabilitation in adults with post-COVID-19 sequelae.

• Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants -
  The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.
  🖺 Full Text HTML: Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants
• Real-time monitoring and analysis of SARS-CoV-2 nanopore sequencing with minoTour. -
  Motivation: The ongoing SARS-CoV-2 pandemic has demonstrated the utility of real-time analysis of sequencing data, with a wide range of databases and resources for analysis now available. Here we show how the real-time nature of Oxford Nanopore Technologies sequencers can accelerate consensus generation, lineage and variant status assignment. We exploit the fact that multiplexed viral sequencing libraries quickly generate sufficient data for the majority of samples, with diminishing returns on remaining samples as the sequencing run progresses. We demonstrate methods to determine when a sequencing run has passed this point in order to reduce the time required and cost of sequencing. Results: We extended MinoTour, our real-time analysis and monitoring platform for nanopore sequencers, to provide SARS-CoV2 analysis using ARTIC network pipelines. We additionally developed an algorithm to predict which samples will achieve sufficient coverage, automatically running the ARTIC medaka informatics pipeline once specific coverage thresholds have been reached on these samples. After testing on run data, we find significant run time savings are possible, enabling flow cells to be used more efficiently and enabling higher throughput data analysis. The resultant consensus genomes are assigned both PANGO lineage and variant status as defined by Public Health England. Samples from within individual runs are used to generate phylogenetic trees incorporating optional background samples as well as summaries of individual SNPs. As minoTour uses ARTIC pipelines, new primer schemes and pathogens can be added to allow minoTour to aid in real- time analysis of pathogens in the future.
  🖺 Full Text HTML: Real-time monitoring and analysis of SARS-CoV-2 nanopore sequencing with minoTour.
• Elucidation of the interactions between SARS-CoV-2 Spike protein and wild and mutant types of IFITM proteins by in silico methods -
  COVID-19 is a viral disease that has been a threat to the whole world since 2019. Although effective vaccines against the disease have been developed, there are still points to be clarified about the mechanism of SARS-CoV-2, which is the causative agent of COVID-19. In this study, we determined the binding energies and the bond types of complexes formed by open (6VYB) and closed (6VXX) forms of the Spike protein of SARS-CoV-2 and wild and mutant forms of IFITM1, IFITM2, and IFITM3 proteins using the molecular docking approach. First, all missense SNPs were found in the NCBI Single Nucleotide Polymorphism database (dbSNP) for IFITM1, IFITM2, and IFITM3 and analyzed with SIFT, PROVEAN, PolyPhen-2, SNAP2, Mutation Assessor, and PANTHER cSNP web-based tools to determine their pathogenicity. When at least four of these analysis tools showed that the SNP had a pathogenic effect on the protein product, this SNP was saved for further analysis. Delta delta G (DDG) and protein stability analysis for amino acid changes were performed in the web-based tools I-Mutant, MUpro, and SAAFEC-SEQ. The structural effect of amino acid change on the protein product was made using the HOPE web-based tool. HawkDock server was used for molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis and binding energies of all complexes were calculated. BIOVIA Discovery Studio program was utilized to visualize the complexes. Hydrogen bonds, salt bridges, and non-bonded contacts between Spike and IFITM protein chains in the complexes were detected with the PDBsum web-based tool. The best binding energy among the 6VYB- IFITM wild protein complexes belong to 6VYB-IFITM1 (-46.16 kcal/mol). Likewise, among the 6VXX-IFITM wild protein complexes, the most negative binding energy belongs to 6VXX-IFITM1 (-52.42 kcal/mol). An interesting result found in the study is the presence of hydrogen bonds between the cytoplasmic domain of the IFITM1 wild protein and the S2 domain of 6VYB. Among the Spike-IFITM mutant protein complexes, the best binding energy belongs to the 6VXX-IFITM2 N63S complex (-50.77 kcal/mol) and the worst binding energy belongs to the 6VXX-IFITM3 S50T complex (4.86 kcal/mol). The study suggests that IFITM1 protein may act as a receptor for SARS-CoV-2 Spike protein. Assays must be advanced from in silico to in vitro for the determination of the receptor-ligand interactions between IFITM proteins and SARS-CoV-2.
  🖺 Full Text HTML: Elucidation of the interactions between SARS-CoV-2 Spike protein and wild and mutant types of IFITM proteins by in silico methods
• Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus- inspired multimerization platform -
  The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.
  🖺 Full Text HTML: Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform
• Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein -
  Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence, though natural selection, of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. These are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate infectivity deficits associated with other non-synonymous substitutions. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain (NTD). Comparatively, very little attention has been directed towards spike insertion mutations. This manuscript describes a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by at least 25 independent acquisitions of 2-8 additional codons between Arg214 and Asp215 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its association with two distinct formerly widespread lineages (A.2.5 and B.1.214.2) and with known VOCs and VOIs warrants further investigation concerning its effects on spike structure and viral infectivity.
  🖺 Full Text HTML: Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
• Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice. -
  The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parental nucleoside of remdesivir, which targets the highly conserved RNA-dependent RNA polymerase. GS-621763 exhibited significant antiviral activity in lung cell lines and two different human primary lung cell culture systems. The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 significantly reduced viral load, lung pathology, and improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral currently in human clinical trial, proved both drugs to be similarly efficacious. These data demonstrate that therapy with oral prodrugs of remdesivir can significantly improve outcomes in SARS-CoV-2 infected mice. Thus, GS-621763 should be explored as a potential treatment for COVID-19 in humans.
  🖺 Full Text HTML: Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.
• A rapid, highly sensitive and open-access SARS-CoV-2 detection assay for laboratory and home testing -
  Global efforts to combat the Covid-19 pandemic caused by SARS-CoV-2 still heavily rely on RT-qPCR-based diagnostic tests. However, their high cost, moderate throughput and reliance on sophisticated equipment limit widespread implementation. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative detection method that has the potential to overcome these limitations. We present a rapid, robust, sensitive and versatile RT- LAMP based SARS-CoV-2 detection assay. Our forty-minute procedure bypasses a dedicated RNA isolation step, is insensitive to carry-over contamination, and uses a hydroxynaphthol blue (HNB)-based colorimetric readout, which allows robust SARS-CoV-2 detection from various sample types. Based on this assay, we have substantially increased sensitivity and scalability by a simple nucleic acid enrichment step (bead-LAMP), established a pipette-free version for home testing (HomeDip-LAMP), and developed open source enzymes that can be produced in any molecular biology setting. Our advanced, universally applicable RT-LAMP assay is a major step towards population-scale SARS-CoV-2 testing.
  🖺 Full Text HTML: A rapid, highly sensitive and open- access SARS-CoV-2 detection assay for laboratory and home testing
• Promise Into Practice: Application of Computer Vision in Empirical Research on Social Distancing -
  Social scientists increasingly use video data, but large-scale analysis of its content is often constrained by scarce manual coding resources. Upscaling may be possible with the application of automated coding procedures, which are being developed in the field of computer vision. Here, we introduce computer vision to social scientists, review the state-of-the-art in relevant subfields, and provide a working example of how computer vision can be applied in empirical sociological work. Our application involves defining a ground truth by human coders, developing an algorithm for automated coding, testing the performance of the algorithm against the ground truth, and run the algorithm on a large- scale dataset of CCTV images. The working example concerns monitoring social distancing behavior in public space over more than a year of the COVID-19 pandemic. Finally, we discuss prospects for the use of computer vision in empirical social science research and address technical and ethical limitations.
  🖺 Full Text HTML: Promise Into Practice: Application of Computer Vision in Empirical Research on Social Distancing
• Parenting During COVID-19: A Sentiment Analysis of Reddit Data -
  The coronavirus disease 2019 (COVID-19) pandemic has caused significant disruption and disturbance in the lives of individuals across the globe. Especially during the early parts of the pandemic, parents took on increased caregiving responsibilities with little to no guidance from health organizations. Further, economic strain made it difficult for parents meet their children’s physical and emotional needs. Much of the research that has examined parenting during COVID-19 has stemmed from survey data. However, self-presentation biases may prevent survey researchers from obtaining authentic and accurate experiences from parents. Therefore, this study examined parents’ sentiment and emotional wellbeing during COVID-19 using Reddit data—specifically, posts from the Mommit and Daddit subreddits. Data were scraped using Python and analyzed in R. Mommit and Daddit subreddits were scraped from March-September 2020, and from March- September 2019 for comparison. Sentiment analysis was conducted using the NRC Word-Emotion Association Lexicon (i.e., EmoLex). Results suggest mothers were more negative than fathers, and mothers expressed more sadness and less trust than fathers. Additionally, mothers were more negative in March 2020 compared to March 2019, while fathers were more negative in April 2020 compared to April 2019. Both mothers and fathers expressed more anticipation in 2020 compared to

2019. Future research should continue to monitor the emotional wellbeing of parents as the COVID-19 pandemic continues.
      🖺 Full Text HTML: Parenting During COVID-19: A Sentiment Analysis of Reddit Data

• Successful Application of Wastewater-Based Epidemiology in Prediction and Monitoring of the Second Wave of COVID-19 in India with Fragmented Sewerage Systems- A Case Study of Jaipur (India) -

  The present study tracked the city-wide dynamics of severe acute respiratory syndrome-corona virus 2 (SARS- CoV-2) RNA in the wastewater from nine different wastewater treatment plants (WWTPs) in Jaipur during second wave of COVID-19 out-break in India. A total of 164 samples were collected weekly between February 19th and June 8th, 2021. SARS-CoV-2 was detected in 47.2% (52/110) influent samples and 37% (20/54) effluent samples. The increasing percentage of positive influent samples correlated with the city increasing active clinical cases during the second wave of COVID-19 in Jaipur. Furthermore, WBE based evidence clearly showed early detection of about 20 days (9/9 samples reported positive on April 20th, 2021) prior to the maximum cases & maximum deaths reported in the city on May 8th,

2021. The present study further observed the presence of SARS-CoV-2 RNA in treated effluents at the time window of maximum active cases in the city even after tertiary disinfection treatments of UV & Chlorine. The average genome concentration in the effluents and removal efficacy of six commonly used treatments; Activated Sludge Treatment + Chlorine disinfection (ASP + Cl2), Moving Bed Biofilm Reactor (MBBR) with Ultraviolet radiations disinfection (MBBR + UV), MBBR + Chlorine (Cl2), Sequencing Batch Reactor (SBR) and SBR + Cl2 were compared with removal efficacy of SBR + Cl2 (81.2%)> MBBR + UV (68.8%) > SBR (57.1%) > ASP (50%) > MBBR + Cl2(36.4%). The study observed the trends & prevalence of four genes (E, RdRp, N, and ORF1ab gene) based on two different kits and found that prevalence of N> ORF1ab >RdRp> E gene, suggested that the effective genome concentration should be calculated based on the presence/absence of multiple genes. Hence, it is imperative to say that using a combination of different detection genes (E, N, RdRp & ORF1ab genes) reduce false positives in WBE.
      🖺 Full Text HTML: Successful Application of Wastewater-Based Epidemiology in Prediction and Monitoring of the Second Wave of COVID-19 in India with Fragmented Sewerage Systems- A Case Study of Jaipur (India)

• Leonardo da Vinci, preregistration and the architecture of science: Towards a more open and transparent research culture -
  There has been much talk of psychological science undergoing a renaissance with recent years being marked by dramatic changes in research practices and to the publishing landscape. This article briefly summarises a number of the ways in which psychological science can improve its rigor, lessen use of questionable research practices and reduce publication bias. The importance of pre-registration as a useful tool to increase transparency of science and improve the robustness of our evidence base, especially in COVID-19 times, is presented. In particular, the case for the increased adoption of Registered Reports, the article format that allows peer review of research studies before the results are known, is outlined. Finally, the article argues that the scientific architecture and the academic reward structure need to change with a move towards “slow science” and away from the “publish or perish” culture.
  🖺 Full Text HTML: Leonardo da Vinci, preregistration and the architecture of science: Towards a more open and transparent research culture
• Citizens’ Attitudes Under Covid19: a cross-country panel survey of public opinion in 11 democracies -

  This article introduces data collected in the Citizens9 Attitudes Under Covid-19 Project (CAUCP), which surveyed public opinion throughout the Covid-19 pandemic in 11 countries between March to December 2020. In this paper, we present a unique cross-country panel survey of citizens9 attitudes and behaviors during a worldwide unprecedented health, governance, and economic crisis. This dataset allows to examine the behavioral and attitudinal consequences of crisis across time and contexts. In this paper, we describe the set-up of the CAUCP and the main features of the dataset and we present promising research prospects.

  🖺 Full Text HTML: Citizens’ Attitudes Under Covid19: a cross-country panel survey of public opinion in 11 democracies
• Determinants of hospital outcomes for COVID-19 infections in a large Pennsylvania Health System -

  There is growing evidence that racial and ethnic minorities bear a disproportionate burden from COVID-19. Temporal changes in the pandemic epidemiology and diversity in the clinical course require careful study to identify determinants of poor outcomes. We analyzed 6255 individuals admitted with PCR-confirmed COVID-19 to one of 5 hospitals in the University of Pennsylvania Health System between March 2020 and March 2021, using electronic health records to assess risk factors and outcomes through 8 weeks post-admission. Discharge, readmission and mortality outcomes were analyzed in a multi-state model with multivariable Cox models for each transition. Mortality varied markedly over time, with cumulative incidence (95% CI) 30 days post-admission of 19.1% (16.9, 21.3) in March-April 2020, 5.7% (4.2, 7.5) in July-October 2020 and 10.5% (9.1,12.0) in January-March 2021; 26% of deaths occurred after discharge. Average age (SD) at admission varied from 62.7 (17.6) to 54.8 (19.9) to 60.5 (18.1); mechanical ventilation use declined from 21.3% to 9-11%. Compared to Caucasian, Black race was associated with more severe disease at admission, higher rates of co- morbidities and low-income resident zip code. Between-race risk differences in mortality risk diminished in multivariable models; while admitting hospital, increasing age, admission early in the pandemic, and severe disease and low blood pressure at admission were associated with increased mortality hazard. Hispanic ethnicity was associated with fewer baseline co-morbidities and lower mortality hazard (0.57, 95% CI: 0.37, .087). Multi-state modeling allows for a unified framework to analyze multiple outcomes throughout the disease course. Morbidity and mortality for hospitalized COVID-19 patients varied over time but post-discharge mortality remained non-trivial. Black race was associated with more risk factors for morbidity and with treatment at hospitals with lower mortality. Multivariable models suggest there are not between-race differences in outcomes. Future work is needed to better understand the identified between- hospital differences in mortality.

  🖺 Full Text HTML: Determinants of hospital outcomes for COVID-19 infections in a large Pennsylvania Health System
• Molecular point-of-care testing for SARS-CoV-2 using the ID NOW(TM) System in Emergency Department: Prospective Evaluation and Implementation in the Care Process -

  Background. The increasing number of cases and hospital admissions due to COVID-19 created an urgent need for rapid, reliable testing procedures for SARS-CoV-2 in Emergency Departments (ED) in order to effectively manage hospital resources, allocate beds and prevent nosocomial spread of infection. The ID NOW(TM) COVID-19 assay is a simple, user- friendly, rapid molecular test run on an instrument with a small footprint enabling point-of-care diagnostics. Methods. In the first wave, outsourced RT-PCR testing regularly required 36-48 hours before results were available. This prospective study was conducted in the second wave (October 2020-April 2021) and evaluated the impact the implementation of the ID NOW(TM) COVID-19 test in the ED had on clinical care processes and patient pathways. 710 patients were recruited upon arrival at the ED which included those presenting clinical symptoms, asymptomatic individuals or persons fulfilling epidemiological criteria. The first anterior nasal swab was taken by trained nurses in the ambulance or a separate consultation room. The ID NOW(TM) COVID-19 test was performed in the ED in strict compliance with the manufacturer9s instructions and positive or suspected cases were additionally tested with RT_PCR (cobas SARS-COV-2 RT- PCR, Roche) following collection of a second nasopharyngeal NP specimen. Results. Swabs directly tested with the ID NOW(TM) COVID-19 test showed a diagnostic concordance of 98 % (sensitivity 99.59 %, specificity 94.55 %, PPV 97.6 %, NPV 99.05 %) compared to RT-PCR as reference. The 488 patients that tested positive with the ID NOW(TM) COVID-19 had a Ct range in RT-PCR results between 7.94 to 37.42 (in 23.2 % > 30). Two false negative results (0.28%) were recorded from patients with Ct values > 30. 14 (1.69%) discordant results were reviewed case-by-case and usually associated with either very early or very advanced stages of infection. Furthermore, patients initially negative with the ID NOW(TM) COVID-19 test and admitted to the hospital were tested again on days 5 and 12: no patient became positive. Discussion. The ID NOW(TM) COVID-19 test for detection of SARS-CoV-2 demonstrated excellent diagnostic agreement with RT-PCR under the above-mentioned patients pathways implemented during the second wave. The main advantage of the system was the provision of reliable results within a few minutes. This not only allowed immediate initiative of appropriate therapy and care for COVID-19 (patient benefit) but provided essential information on isolation and thus available beds. This drastically helped the overall finances of the department and additionally allowed more patients to be admitted including those requiring immediate attention; this was not possible during the first wave since beds were blocked waiting for diagnostic confirmation. Our findings also show that when interpreting the results, the clinical condition and epidemiological history of the patient must be taken into account, as with any test procedure. Overall, the ID NOW(TM) COVID-19 test for SARS-CoV-2 provided a rapid and reliable alternative to laboratory-based RT-PCR in the real clinical setting which became an acceptable part of the daily routine within the ED and demonstrated that early patient management can mitigate the impact of the pandemic on the hospital.

  🖺 Full Text HTML: Molecular point-of-care testing for SARS-CoV-2 using the ID NOW(TM) System in Emergency Department: Prospective Evaluation and Implementation in the Care Process

From Clinical Trials

• High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition:   Covid19
  Interventions:   Drug: High doses of intravenous vitamin C;   Drug: Dextrose 500 mL
  Sponsor:   Hugo Galindo
  Not yet recruiting

• Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) - Condition:   COVID-19
  Interventions:   Drug: Favipiravir;   Drug: Monoclonal antibodies;   Drug: Ivermectin;   Other: No treatment;   Drug: Remdesivir
  Sponsor:   University of Oxford
  Not yet recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition:   COVID-19 Respiratory Infection
  Intervention:   Drug: Vitamin D
  Sponsor:   Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
  Completed

• Text Message Nudges for COVID-19 Vaccination - Condition:   Covid19
  Intervention:   Behavioral: Text message
  Sponsor:  
  Ascension South East Michigan
  Not yet recruiting

• A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid - Condition:   COVID-19
  Intervention:   Behavioral: Physiotherapy
  Sponsors:  
  University of Calgary;   Alberta Health Services
  Not yet recruiting

• Quercetin in the Prevention of Covid-19 Infection - Condition:   Covid19
  Interventions:   Dietary Supplement: Quercetin;   Combination Product: Placebo
  Sponsor:   Azienda di Servizi alla Persona di Pavia
  Completed

• A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition:   Covid19
  Intervention:   Drug: OPN-019
  Sponsor:   Optinose US Inc.
  Recruiting

• Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition:   Covid19
  Interventions:   Behavioral: Physical activity;   Other: Smell training
  Sponsor:   Université de Montréal
  Not yet recruiting

• Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: CoVLP formulation
  Sponsor:  
  Medicago
  Not yet recruiting

• Safety and Efficacy of KOVIR in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Drug: KOVIR oral capsule;   Drug: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Big Leap Clinical Research Joint Stock Company
  Active, not recruiting

• Evaluation of the Efficacy, Safety and Immunogenicity of Inactivated COVID 19 Vaccine(TURKOVAC) in Healthy Population of 18 and 64 Years of Age (Both Inclusive):a Randomized, Double-blind, Phase IIb Clinical Trial - Condition:   Covid19
  Intervention:   Biological: Triple dose vaccination by inactivated Covid19 vaccine
  Sponsors:   Health Institutes of Turkey;   TC Erciyes University;   Kocak Farma;   Mene Research
  Not yet recruiting

• Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue - Condition:   COVID-19 Respiratory Infection
  Intervention:  
  Other: Cardiopulmonary exercise training
  Sponsor:   Louis Bherer
  Recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell);   Biological: COVID-19 vaccine (Vero cells)
  Sponsors:  
  National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Abbott ID NOW COVID-19 - Conditions:   Covid19;   SARS-CoV-2 Infection
  Interventions:  
  Diagnostic Test: Buccal Swab- Copan flocked swab;   Diagnostic Test: Standard of Care COVID-19 swab
  Sponsors:   University of Calgary;   Health Canada
  Not yet recruiting

From PubMed

• Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against…

• Dehydrozingerone ameliorates Lipopolysaccharide induced acute respiratory distress syndrome by inhibiting cytokine storm, oxidative stress via modulating the MAPK/NF-kappaB pathway - CONCLUSION: This study demonstrates for the first time that DHZ has the potential to ameliorate LPS induced ARDS by inhibiting cytokine storm and oxidative through modulating the MAPK and NF-κB pathways. This data provides pre-clinical support to develop DHZ as a potential therapeutic agent against ARDS.

• Genomics-guided targeting of stress granule proteins G3BP1/2 to inhibit SARS-CoV-2 propagation - SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced phase separation (LLPS) and sequesters the host key stress granule (SG) proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and 2 (G3BP1 and G3BP2) to inhibit SG formation. This will allow viral packaging and propagation in host cells. Based on a genomic-guided meta-analysis, here we identify upstream regulatory elements modulating the expression of G3BP1 and G3BP2 (collectively called G3BP1/2). Using this strategy, we…

• Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2 - Apart from the canonical fingers, palm and thumb domains, the RNA dependent RNA polymerases (RdRp) from the viral order Nidovirales possess two additional domains. Of these, the function of the Nidovirus RdRp associated nucleotidyl transferase domain (NiRAN) remains unanswered. The elucidation of the 3D structure of RdRp from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), provided the first ever insights into the domain organisation and possible functional characteristics of…

• SARS-COV-2 M(pro) conformational changes induced by covalently bound ligands - SARS-CoV-2’s main protease (M^(pro)) interaction with ligands has been explored with a myriad of crystal structures, most of the monomers. Nonetheless, M^(pro) is known to be active as a dimer but the relevance of the dimerization in the ligand-induced conformational changes has not been fully elucidated. We systematically simulated different M^(pro)-ligand complexes aiming to study their conformational changes and interactions, through molecular dynamics (MD). We focused on covalently bound…

• Targeted Redesign of Suramin Analogs for Novel Antimicrobial Lead Development - The emergence of new viral infections and drug-resistant bacteria urgently necessitates expedient therapeutic development. Repurposing and redesign of existing drugs against different targets are one potential way in which to accelerate this process. Suramin was initially developed as a successful antiparasitic drug but has also shown promising antiviral and antibacterial activities. However, due to its high conformational flexibility and negative charge, suramin is considered quite promiscuous…

• Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic - BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide.

• Incorporation efficiency and inhibition mechanism of 2’-substituted nucleotide analogs against SARS-CoV-2 RNA- dependent RNA polymerase - The ongoing pandemic caused by SARS-CoV-2 emphasizes the need for effective therapeutics. Inhibition of SARS-CoV-2 RNA- dependent RNA polymerase (RdRp) by nucleotide analogs provides a promising antiviral strategy. One common group of RdRp inhibitors, 2’-modified nucleotides, are reported to exhibit different behaviors in the SARS-CoV-2 RdRp transcription assay. Three of these analogs, 2’-O-methyl UTP, Sofosbuvir, and 2’-methyl CTP, act as effective inhibitors in previous biochemical experiments,…

• Zinc(2+) ion inhibits SARS-CoV-2 main protease and viral replication in vitro - Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with zinc demonstrate better clinical outcomes. The molecular targets and mechanistic details of the anti-coronaviral activity of zinc remain obscure. We show that zinc not only inhibits the SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of the Mpro-Zn^(2+) complex at 1.9 Å and provide the structural basis of viral replication…

• Peptide-Based Inhibitors for SARS-CoV-2 and SARS-CoV - The COVID-19 (coronavirus disease) global pandemic, caused by the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti-virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS-CoV-2, and can be readily modified to match viral mutation rate. A recent expansion of the…

• Identification of novel transmembrane Protease Serine Type 2 drug candidates for COVID-19 using computational studies - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergence has resulted in a global health crisis. As a consequence, discovering an effective therapy that saves lives and slows the spread of the pandemic is a global concern currently. In silico drug repurposing is highly regarded as a precise computational method for obtaining fast and reliable results. Transmembrane serine-type 2 (TMPRSS2) is a SARS CoV-2 enzyme that is essential for viral fusion with the host cell. Inhibition of…

• Computational approach towards the design of artemisinin-thymoquinone hybrids against main protease of SARS-COV-2 - CONCLUSIONS: Hybrid products of artemisinin and thymoquinone have the potential to inhibit Mpro, with desirable pharmacokinetic and toxicity characteristics compared to commercially available drugs, being indicated for preclinical and subsequent clinical studies against SARS-CoV-2. Emphasizing the possibility of synergistic use with currently used drugs in order to increase half-life and generate a possible synergistic effect. This work represents an important step for the development of…

• Potential Immunomodulatory Properties of Biologically Active Components of Spices Against SARS-CoV-2 and Pan beta- Coronaviruses - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced COVID-19 has emerged as a defining global health crisis in current times. Data from the World Health Organization shows demographic variations in COVID-19 severity and lethality. Diet may play a significant role in providing beneficial host cell factors contributing to immunity against deadly SARS-CoV-2 pathogenesis. Spices are essential components of the diet that possess anti- inflammatory, antioxidant, and antiviral…

• SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis With the Assistance of Nucleocapsid Protein N in Cells - The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don’t know how specific SARS- CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via…

• Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pandemic - In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and…

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• SARS-COV-2 BINDING PROTEINS - - link

• COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

• 一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link