Covid-19 Sentry

Contents

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

From Preprints

• Platelet proteome analysis reveals an early hyperactive phenotype in SARS-CoV-2-infected humanized ACE2 mice -
  Coronavirus disease-2019 (COVID-19) provokes a hypercoagulable state with increased incidence of thromboembolism and mortality. Platelets are major effectors of thrombosis and hemostasis. Suitable animal models are needed to better understand COVID-19-associated coagulopathy (CAC) and underlying platelet phenotypes. Here, we assessed K18-hACE2 mice undergoing a standardized SARS-CoV-2 infection protocol to study dynamic platelet responses via mass spectrometry-based proteomics. In total, we found significant changes in >1,200 proteins. Strikingly, protein alterations occurred rapidly by 2 days post-infection (dpi) and preceded outward clinical signs of severe disease. Pathway enrichment analysis of 2dpi platelet proteomes revealed that SARS-CoV-2 infection upregulated complement-coagulation networks (F2, F12, CFH, CD55/CD59), platelet activation-adhesion-degranulation proteins (PF4, SELP, PECAM1, HRG, PLG, vWF), and chemokines (CCL8, CXCL5, CXCL12). When mice started to lose weight at 4dpi, pattern recognition receptor signaling (RIG-I/MDA5, CASP8, MAPK3), and interferon pathways (IFIT1/IFIT3, STAT1) were predominant. Interestingly, SARS-CoV-2 spike protein in the lungs was observed by immunohistochemistry, but in platelets was undetected by proteomics. Similar to patients, K18-hACE2 mice during SARS-CoV-2 infection developed progressive lymphohistiocytic interstitial pneumonia with platelet aggregates in the lungs and kidneys. In conclusion, this model recapitulates activation of coagulation, complement, and interferon responses in circulating platelets, providing valuable insight into platelet pathology during COVID-19.
  🖺 Full Text HTML: Platelet proteome analysis reveals an early hyperactive phenotype in SARS-CoV-2-infected humanized ACE2 mice
• High-Spatiotemporal-Resolution Nanopore Sequencing of SARS-CoV-2 and Host Cell RNAs -
  Recent studies have disclosed the genome, transcriptome and epigenetic compositions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the effect of viral infection on gene expression of the host cells. It has been demonstrated that, besides the major canonical transcripts, the viral genome also codes for non-canonical RNA molecules. While the structural characterizations have revealed a detailed transcriptomic architecture of the virus, the kinetic studies provided poor and often misleading results on the dynamics of both the viral and host transcripts due to the low temporal resolution of the infection event and the low virus/cell ratio (MOI=0.1) applied for the infection. In this study, we used direct cDNA and direct RNA nanopore sequencings for the generation of high-coverage, high-temporal- resolution transcriptomic datasets on SARS-CoV-2 and on primate host cells infected with a high virus titer (MOI=5). Sixteen sampling time points ranging from 1 to 96h with a varying time resolution and three biological replicates were used in the experiment for both the infected and the non-infected cells.
  🖺 Full Text HTML: High- Spatiotemporal-Resolution Nanopore Sequencing of SARS-CoV-2 and Host Cell RNAs
• Identification of a conserved neutralizing epitope present on spike proteins from all highly pathogenic coronaviruses -
  Three pathogenic human coronaviruses have emerged within the last 20 years, with SARS-CoV-2 causing a global pandemic. Although therapeutic antibodies targeting the SARS-CoV-2 spike currently focus on the poorly conserved receptor-binding domain, targeting essential neutralizing epitopes on the more conserved S2 domain may provide broader protection. We report an antibody binding an epitope conserved in the pre-fusion core of MERS-CoV, SARS-CoV and SARS- CoV-2 spike S2 domains. Antibody 3A3 binds a conformational epitope with ~2.5 nM affinity and neutralizes spike from SARS-CoV, SARS-CoV-2 and variants of concern in in vitro pseudovirus assays. Hydrogen-deuterium exchange mass spectrometry identified residues 980-1006 in the flexible hinge region at the S2 apex as the 3A3 epitope, suggesting 3A3 prevents the S2 conformational rearrangements required for conversion to the spike post-fusion state and virus-host cell fusion. This work defines a conserved vulnerable site on the SARS-CoV-2 S2 domain and guides the design of pan- protective spike immunogens.
  🖺 Full Text HTML: Identification of a conserved neutralizing epitope present on spike proteins from all highly pathogenic coronaviruses
• Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway. -
  SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.
  🖺 Full Text HTML: Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.
• The association between immunosuppressants use and COVID-19 adverse outcome: National COVID-19 cohort in South Korea -

  Background: There is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure), and COVID-19 patient outcomes. Methods: We conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals, comparing immunosuppressants users and non-users. Findings: We identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,903 were non-users. Patients who used immunosuppressants were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use (IPTW OR 1.32; 95% CI: 1.06 - 1.63). Patients who used corticosteroids were at increased odds of the primary outcome (IPTW OR 1.33; 95% CI: 1.07 - 1.64). Interpretation: We support the latest guidelines from the CDC, that people on immunosuppressants are at high risk of severe COVID-19 and immunocompromised people may need booster COVID-19 vaccinations.

  🖺 Full Text HTML: The association between immunosuppressants use and COVID-19 adverse outcome: National COVID-19 cohort in South Korea
• Changes in the serial interval and transmission dynamics associated with the SARS-CoV-2 Delta variant in South Korea -

  We estimated the mean serial interval and superspreading potential for the Delta variant SARS-CoV-2. As the Delta variant increased in prevalence, the mean serial interval declined from 4.0 to 2.5 days. However, the risk of superspreading events was similar, as 25% to 27% of cases seeded 80% of all transmission.

  🖺 Full Text HTML: Changes in the serial interval and transmission dynamics associated with the SARS-CoV-2 Delta variant in South Korea
• COVID-19 Incidence and Hospitalization Rates are Inversely Related to Vaccination Coverage Among the 112 Most Populous Counties in the United States -

  We tested whether COVID-19 incidence and hospitalization rates were inversely related to vaccination coverage among the 112 most populous counties in the United States, each with a population exceeding 600,000. We measured vaccination coverage as the percent of the total population fully vaccinated as of July 15, 2021, with the exception of 11 Texas counties, where the cutoff date was July 14, 2021. We measured COVID-19 incidence as the number of confirmed cases per 100,000 population during the 14-day period ending August 12, 2021. We measured hospitalization rates as the number of confirmed COVID-19 admissions per 100,000 population during the same 14-day period. COVID-19 incidence was significantly higher among counties in the lower half of the distribution of vaccination coverage (incidence 543.8 per 100,000 among 56 counties with mean coverage 42.61%) than among counties in the lower half of the distribution of coverage (incidence 280.7 per 100,000 among 56 counties with mean coverage 57.37%, p < 0.0001). Hospital admissions were also significantly higher among counties in the lower half of the distribution (55.37 per 100,000) than in the upper half of the distribution (20.48 per 100,000, p < 0.0001). In log-linear regression models, a 10-percentage- point increase in vaccination coverage was associated with a 28.3% decrease in COVID-19 incidence (95% confidence interval, 16.8 - 39.7%), a 44.9 percent increase in the rate of COVID-19 hospitalization (95% CI, 28.8 - 61.0%), and a 16.6% decrease in COVID-19 hospitalizations per 100 cases (95% CI, 8.4 - 24.8%). Higher vaccination coverage is associated not only with significantly lower COVID-19 incidence, but also significantly less severe cases of the disease.

  🖺 Full Text HTML: COVID-19 Incidence and Hospitalization Rates are Inversely Related to Vaccination Coverage Among the 112 Most Populous Counties in the United States
• COVID-19 infection, hospitalisation and death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project. -

  Objectives: To calculate the rates of COVID19 infection and COVID19 related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID19 pandemic in England compared to the general population. Methods: We used Hospital Episode Statistics to identify all people alive 01 March 2020 with ICD10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID19 infection and death up to 31 July 2020. Our primary definition of COVID19 related death was mention of COVID19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID19 related hospital admissions and all cause deaths. Results: We identified a cohort of 168,680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID19 PCR test. The age standardised infection rate was 1.54 (95% CI 1.50, 1.59) times higher than in the general population. 713 (0.42%) people with RAIRD died with COVID19 on their death certificate and the age sex standardised mortality rate for COVID19 related death was 2.41 (2.30, 2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. Conclusions: During the first wave of COVID19 in England, people with RAIRD had a 54% increased risk of COVID19 infection and more than twice the risk of COVID19 related death compared to the general population. These increases were seen despite shielding policies.

  🖺 Full Text HTML: COVID-19 infection, hospitalisation and death Amongst People with Rare Autoimmune Rheumatic Disease in England. Results from the RECORDER Project.
• Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities -

  OBJECTIVES. Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODS. People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS. The 226 primary cases were followed by 197 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 35% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.92). SIR was 56% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.54; 95% CI 1.03-2.31). SIR was highest among primary case-contacts pairs aged ≥65 years (77%) and 5-11 years (70%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS. Both children and adults can transmit and are susceptible to SARS- CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.

  🖺 Full Text HTML: Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities
• Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination -

  High COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 84% over 6 months time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 70% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.

  🖺 Full Text HTML: Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination
• RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from asymptomatic and symptomatic individuals -

  To validate an improved sample preparation method for extraction free Direct RT-LAMP and define the clinical performance of four different RT-LAMP assay formats for detection of SARS-CoV-2 with a multisite clinical evaluation. We describe Direct RT-LAMP on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples collected from asymptomatic and symptomatic individuals across multiple healthcare and community settings. For Direct RT-LAMP, we found a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) of 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT-qPCR ORF1ab CT values of<25 and <33 (high and medium-high viral copy number, respectively), we found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) and 87.32% (80.71-92.31%) for saliva. For RNA RT-LAMP DSe and DSp were 95.98% (92.74-98.06%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. The findings from these evaluations demonstrate that RT-LAMP testing of swabs and saliva is applicable to a variety of different use-cases, including frequent, interval-based testing of saliva from asymptomatic individuals via Direct RT-LAMP that may otherwise be missed using symptomatic testing alone.

  🖺 Full Text HTML: RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from asymptomatic and symptomatic individuals
• Association of COVID-19 vaccination with risks of hospitalization and mortality due to cardiovascular and other diseases: A study of the UK Biobank -

  Background Vaccines for COVID-19 represent a breakthrough in the fight against the pandemic. However, worries about adverse effects have led to vaccine hesitancy in some people. On the other hand, as COVID-19 may be associated with a range of sequelae, it is possible that vaccines may protect against hospitalization and mortality of various diseases. Methods We leveraged a large prospective cohort, the UK-Biobank (UKBB), and studied associations of at least one dose of COVID-19 vaccination (BioNTech BNT162b2 or Oxford-AstraZeneca ChAdOx1 nCoV-19) with hospitalization and mortalities from cardiovascular and other diseases (N=180,727). Multivariable Cox and Poisson regression was conducted controlling for main confounders. For hospitalizations, we also conducted separate analysis for new-onset and recurrent cases. All-cause and cardiovascular mortality were also included as outcome. Results We observed that COVID-19 vaccination (at least one dose) was associated with lower risks of hospitalizations from stroke (hazard ratio [HR]=0.371, 95% CI: 0.254-0.543, p=3.36e-7), venous thromboembolism (VTE) (HR=0.485, 95% CI: 0.292-0.804, p=4.99e-3), dementia (HR=0.207, 95% CI 0.091-0.470; p=1.66e-4) and non-COVID-19 pneumonia (HR=0.482, 95% CI 0.313-0.742; p=9.18e-4). Regarding mortality, an association with lower all-cause and cardiovascular mortality was observed, as well as lower mortality from several diseases including stroke, coronary artery disease(CAD), and chronic obstructive pulmonary disease (COPD) and dementia. There is no evidence that vaccination was associated with increased hospitalization/fatality from any specific disorders. Conclusions Taken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. As an observational study, causal relationship cannot be concluded and further studies are required to verify the findings.

  🖺 Full Text HTML: Association of COVID-19 vaccination with risks of hospitalization and mortality due to cardiovascular and other diseases: A study of the UK Biobank
• Diminishing immune responses against variants of concern in dialysis patients four months after SARS-CoV-2 mRNA vaccination -

  Patients undergoing chronic hemodialysis were among the first to receive SARS-CoV-2 vaccinations due to their increased risk for severe COVID-19 disease and high case fatality rates. To date, there have been minimal longitudinal studies in hemodialysis patients to ascertain whether protection offered by vaccination is long-lasting. To assess how surrogates for protection changed over time, we examined both the humoral and cellular response in a previously reported cohort of at-risk hemodialysis patients and healthy donors, four months after their second dose of Pfizer BNT162b2. Compared to three weeks post-second vaccination, both cellular and humoral responses against the original SARS-CoV-2 isolate as well as variants of concern were significantly reduced, with some dialyzed individuals having no B- or T-cell response. Our data strongly support the need for a third booster in hemodialysis patients and potentially other at-risk individuals.

  🖺 Full Text HTML: Diminishing immune responses against variants of concern in dialysis patients four months after SARS-CoV-2 mRNA vaccination
• COVID-19 ASSOCIATED MUCORMYCOSIS: A CASE-CONTROL STUDY -

  Background: India has seen a surge in COVID-19 associated mucormycosis (CAM) cases during the second wave of the pandemic. We conducted a study to determine independent risk factors for CAM. Methods: We performed a retrospective case control study in a tertiary care private hospital in Pune, India. Fifty-two cases of CAM were compared with 166 concurrent controls randomly selected from the COVID-19 admissions during the same time period. Association of demographic factors, comorbidities, cumulative steroid dose used (calculated as dexamethasone equivalent), maximum respiratory support required, use of injectable/oral anticoagulation, and use of aspirin with CAM was assessed by univariate and multivariate logistic regression. Results: A total of 218 subjects (52 cases; 166 controls) were studied. Any diabetes (pre-existing diabetes and new onset diabetes during COVID-19) was noted in a significantly higher proportion of cases (73.1%, 45.8% P<0.001) and cumulative dexamethasone dose used in cases was significantly greater (97.72 mg vs 60 mg; P=0.016). In a multivariate regression analysis cumulate dexamethasone dose >120 mg (OR 9.03, confidence interval 1.75-46.59, P=0.009) and any diabetes (OR 4.78, confidence interval 1.46-15.65, P=0.01) were found to be risk factors for CAM. While use of anticoagulation (OR 0.01, confidence interval 0.00-0.09, P<0.001) and use of aspirin (OR 0.02, confidence interval 0.01-0.07, P<0.001) were found to be protective against CAM. Conclusion: Diabetes mellitus and cumulative dose of dexamethasone greater than 120 mg (or equivalent dose of other corticosteroid) were associated with an increased risk of CAM while use of aspirin and anticoagulation were associated with a lower risk.

  🖺 Full Text HTML: COVID-19 ASSOCIATED MUCORMYCOSIS: A CASE-CONTROL STUDY
• The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale -

  Throughout the course of the ongoing SARS-CoV-2 pandemic there has been a need for approaches that enable rapid monitoring of public health using an unbiased and minimally invasive means. A major way this has been accomplished is through the regular assessment of wastewater samples by qRT-PCR to detect the prevalence of viral nucleic acid with respect to time and location. Further expansion of SARS-CoV-2 wastewater monitoring efforts to include the detection of variants of interest / concern through next-generation sequencing have enhanced the understanding of the SARS-CoV-2 outbreak. In this report we detail the results of a collaborative effort between public health and metropolitan wastewater management authorities and the University of Louisville to monitor the SARS-CoV-2 pandemic through the monitoring of aggregate wastewater samples over a period of 28 weeks. Our data indicates that wastewater monitoring of water quality treatment centers and smaller neighborhood-scale catchment areas is a viable means by which the prevalence and genetic variation of SARS-CoV-2 within a metropolitan community of approximately one million individuals may be monitored. Importantly, these efforts confirm that regional emergence and spread of variants of interest / concern may be detected as readily in aggregate wastewater samples as compared to the individual wastewater sheds.

  🖺 Full Text HTML: The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale

From Clinical Trials

• Pulmonary Rehabilitation Post-COVID-19 - Condition:   COVID-19
  Intervention:   Other: Exercise program (virtual/remote)
  Sponsors:   University of Manitoba;   Health Sciences Centre Foundation, Manitoba;   Health Sciences Centre, Winnipeg, Manitoba
  Not yet recruiting

• A Study of PF-07321332/Ritonavir in Non-hospitalized Low-Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique - Condition:   Covid19
  Interventions:   Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell);   Biological: AZD1222 (replication-deficient Ad type 5 vector expressing full-length spike protein)
  Sponsors:   International Vaccine Institute;   The Coalition for Epidemic Preparedness Innovations (CEPI);   Instituto Nacional de Saúde (INS), Mozambique;   University of Antananarivo;   International Centre for Diarrhoeal Disease Research, Bangladesh;   Harvard University;   Heidelberg University
  Not yet recruiting

• Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease - Condition:   COVID-19
  Intervention:   Drug: leflunomide
  Sponsor:  
  Ashford and St. Peter’s Hospitals NHS Trust
  Active, not recruiting

• COVID-19 Methylene Blue Antiviral Treatment - Condition:   Covid19
  Interventions:   Drug: Methylene Blue;   Drug: Saline nasal spray
  Sponsors:   Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences;   Irkutsk State Medical University
  Recruiting

• Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Other: Placebo control
  Sponsors:   WestVac Biopharma Co., Ltd.;   West China Hospital
  Not yet recruiting

• To Evaluate Efficacy & Safety of Proxalutamide in Hospitalized Covid-19 Subjects - Condition:   Covid19
  Interventions:   Drug: GT0918;   Drug: Standard of care;   Drug: Matching placebo
  Sponsors:   Suzhou Kintor Pharmaceutical Inc,;   IQVIA Biotech
  Not yet recruiting

• Double Blind Randomized Clinical Trial of Use of Colchicine Added to Standard Treatment in Hospitalized With Covid-19 - Condition:   COVID-19 Infection
  Intervention:   Drug: Colchcine
  Sponsor:  
  Asociacion Instituto Biodonostia
  Active, not recruiting

• Relaxation Exercise in Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: Relaxation technique
  Sponsor:   Beni- Suef University
  Completed

• Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19 - Condition:   Covid19
  Interventions:   Combination Product: Favipiravir + Standard of Care;   Procedure: Standard of Care
  Sponsors:   University of the Philippines;   Department of Health, Philippines
  Recruiting

• Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition:   Covid19
  Interventions:   Drug: Standard of care;   Dietary Supplement: combination of curcumin, quercetin and Vitamin D
  Sponsor:   Ayub Teaching Hospital
  Not yet recruiting

• Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study). - Condition:   Covid19
  Interventions:   Drug: C1 Inhibitor Human;   Drug: Icatibant Injection;   Other: Placebo
  Sponsor:   GCS Ramsay Santé pour l’Enseignement et la Recherche
  Completed

• A Study to Evaluate the Safety and Efficacy of Artemisinin- a Herbal Supplement on COVID-19 Subjects - Condition:   Covid19
  Interventions:   Dietary Supplement: Artemisinin;   Drug: Dexamethasone
  Sponsors:   Mateon Therapeutics;   Windlas Biotech Private Limited
  Completed

• Clinical Trial to Assess the Efficacy and Safety of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms - Condition:   Covid19
  Intervention:   Drug: Drug, inhalation
  Sponsor:  
  Aquilon Pharmaceuticals S.A.
  Not yet recruiting

• Local and General Immune Response After Coronavirus Disease (COVID-19) Vaccination in Volunteers - Condition:   Covid19
  Intervention:   Procedure: Blood and nasal fluid sampling before and after COVID-19 vaccination
  Sponsors:   University Hospital, Ghent;   University Ghent;   Vlaams Instituut voor Biotechnologie
  Active, not recruiting

From PubMed

• OFF-State-Specific Inhibition of the Proprotein Convertase Furin - The pro-protein convertase furin is a highly specific serine protease involved in the proteolytic maturation of many proteins in the secretory pathway. It also activates surface proteins of many viruses including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furin inhibitors effectively suppress viral replication and thus are promising antiviral therapeutics with broad application potential. Polybasic substrate-like ligands typically trigger conformational changes shifting…

• Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study - The epidemiologic correlation between the poor prognosis of SARS-CoV-2 infection and vitamin D deficiency has been observed worldwide, however, their molecular mechanisms are not fully understood. In this study, we used combined molecular docking, molecular dynamics simulations and binding free energy analyses to investigate the potentials of vitamin D3 and its hydroxyderivatives as TMPRSS2 inhibitor and to inhibit the SARS-CoV-2 receptor binding domain (RBD) binding to angiotensin-converting…

• Probing the Allosteric Inhibition Mechanism of a Spike Protein Using Molecular Dynamics Simulations and Active Compound Identifications - The receptor recognition of the novel coronavirus SARS-CoV-2 relies on the “down-to-up” conformational change in the receptor-binding domain (RBD) of the spike (S) protein. Therefore, understanding the process of this change at the molecular level facilitates the design of therapeutic agents. With the help of coarse-grained molecular dynamic simulations, we provide evidence showing that the conformational dynamics of the S protein are globally cooperative. Importantly, an allosteric path was…

• Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8 - This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll-like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double-blind, placebo- controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single-dose cohorts received one…

• MicroRNA-28-3p inhibits angiotensin-converting enzyme 2 ectodomain shedding in 293T cells treated with the spike protein of severe acute respiratory syndrome coronavirus 2 by targeting A disintegrin and metalloproteinase 17 - Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus that causes coronavirus disease 2019. Angiotensin‑converting enzyme 2 (ACE2) is the SARS‑CoV binding site and is ubiquitously expressed in endothelial cells of several organs, with the highest levels in the cardiovascular system, kidney and lungs. A disintegrin and metalloproteinase 17 (ADAM17) is involved in ectodomain shedding of ACE2. In the present study, reverse‑transcription‑quantitative PCR, transfection, TUNNEL…

• Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir - SARS-CoV-2 main protease (M^(pro)) is a cysteine protease that mediates the cleavage of viral polyproteins and is a validated antiviral drug target. M^(pro) is highly conserved among all seven human coronaviruses, with certain M^(pro) inhibitors having broad-spectrum antiviral activity. In this study, we designed two hybrid inhibitors UAWJ9-36-1 and UAWJ9-36-3 based on the superimposed X-ray crystal structures of SARS-CoV-2 M^(pro) with GC-376, telaprevir, and boceprevir. Both UAWJ9-36-1 and…

• Poliovirus Vaccination Induces a Humoral Immune Response That Cross Reacts With SARS-CoV-2 - Background: Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2. Methods: Publicly available data were analyzed for possible correlations between national median ages and…

• Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide - CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45…

• Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19 - The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly identified and translated to clinical care. Traditional drug discovery methods have a >90% failure rate and can take 10 to 15 y from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious…

• An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19) - INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment.

• Efficient inactivation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in human apheresis platelet concentrates with amotosalen and ultraviolet A light - CONCLUSION: SARS-CoV-2 was efficiently inactivated in platelet concentrates by amotosalen/UVA treatment. These results are in line with previous inactivation data for SARS-CoV-2 in plasma as well as MERS-CoV and SARS-CoV-1 in platelets and plasma, demonstrating efficient inactivation of human coronaviruses.

• Osteopathic interventions via telehealth in a pediatric population: a retrospective case series - CONCLUSIONS: In our small retrospective case series, osteopathic interventions via telehealth resulted in decreased average pain scores following treatment while minimizing risk of viral exposure and transmission. Further study is needed to determine if such treatment methods could be effective on a larger scale when distance or illness preclude an in-person OMT visit.

• Deconstructing the Treatment Effect of Remdesivir in the Adaptive COVID-19 Treatment Trial-1: Implications for Critical Care Resource Utilization - CONCLUSIONS: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.

• Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency - Non-covalent inhibitors of the main protease (M^(pro)) of SARS-CoV-2 having a pyridinone core were previously reported with IC(50) values as low as 0.018 μM for inhibition of enzymatic activity and EC(50) values as low as 0.8 μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of M^(pro) and N-methylation of a uracil ring. Free energy perturbation…

• Long Noncoding RNAs as Emerging Regulators of COVID-19 - Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus…

From Patent Search

• SARS-COV-2 BINDING PROTEINS - - link

• 자외선살균등 - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - link

• A Protein chip and kit for detecting SARS-CoV-2 N protein and its preparation method - - link

• Protein chip and kit for detecting the SARS-CoV-2 S antigen - - link

• Cabina de desinfección de doble carga exterior - - link

• A Novel Method COVID -19 infection using Deep Learning Based System - - link

• 一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗 - 本发明适用于生物技术领域，提供了一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗，该表达载体的构建方法包括以下步骤：将表达新冠病毒S蛋白与NP蛋白的核苷酸序列使用2A肽进行连接，合成融合基因；在融合基因的两端分别包含两个酶切位点，并装载到质粒，得到重组质粒；对重组质粒进行双酶切，切胶回收目的基因片段；对原始的质粒进行双酶切，切胶回收载体片段；将目的基因片段和载体片段进行连接，得到所述表达载体。本发明实施例通过同时表达冠状病毒S蛋白受体结合区与NP蛋白，使该表达载体感染的细胞不但可以诱导抗体反应还能诱导T细胞反应，从而有效诱导体液免疫和细胞免疫，为受试者提供更强的免疫保护。 - link

• EMPUNADURA DE RAQUETA O PALA PARA JUEGO DE PELOTA CON DISPENSADOR LIQUIDO POR CAPILARIDAD INSERTADO - - link

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• System zum computergestützten Nachverfolgen einer von einer Person durchzuführenden Prozedur -

  Ein System (2000) zum computergestützten Nachverfolgen einer von einer Person (1) durchzuführenden Testprozedur, insbesondere für einen Virusnachweistest, bevorzugt zur Durchführung eines SARS-CoV-2 Tests, wobei das System (2000) umfasst:

• eine Identifizierungseinheit eines Endgeräts (30), die eingerichtet ist zum Identifizieren (201) der Person

1. unmittelbar vor einem Durchführen der Testprozedur durch die Person (1);

• wobei die Identifizierungseinheit des Endgeräts (30) weiter eingerichtet ist zum Identifizieren (202) zumindest eines Testobjekts (20), bevorzugt einer Testkassette, insbesondere für einen SARS-CoV-2 Test, mehr bevorzugt eines Teststreifens, weiter bevorzugt ein Reagenz in einem Behälter, weiter bevorzugt eines Testsensors, unmittelbar vor der Durchführung der Testprozedur, die Identifizierungseinheit aufweisend:
• eine Kamera (31) des Endgeräts (30), eingerichtet zum Erfassen (2021) eines Objektidentifizierungsdatensatzes (21) als maschinenlesbaren Datensatz; und
• eine Auswerteeinheit (33) des Endgeräts (30), eingerichtet zum Vergleichen (2022) des erfassten Objektidentifizierungsdatensatzes (21) mit einem Objektdatensatz

420. eines Hintergrundsystems (40);

• eine Nachverfolgungseinheit des Endgeräts (30), die eingerichtet ist zum Nachverfolgen (203) einer oder mehrerer Positionen der Person (1) während der Durchführung der Testprozedur mittels Methoden computergestützter Gesten- und/oder Muster- und/oder Bilderkennung mittels eines Prüfens, ob beide Hände (12) der Person (1) während der gesamten Durchführung der Testprozedur in einem vordefinierten Bereich oder einem von der Kamera (31a) des Endgeräts (30) erfassbaren Bereich sind;
• die Nachverfolgungseinheit des Endgeräts (30), zudem eingerichtet zum Nachverfolgen (203) von einer oder mehreren Positionen des zumindest einen Testobjekts (20) anhand der Form des Objekts während der Durchführung der Testprozedur mittels Methoden computergestützter Gesten- und/oder Muster- und/oder Bilderkennung; und
• einer Anzeigeeinheit (34) des Endgeräts, eingerichtet zum Anleiten (204) der Person (1) zum Durchführen der Testprozedur während der Durchführung der Testprozedur.

• link