Covid-19 Sentry

Contents

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

From Preprints

• Alpha-ketoglutarate augments prolyl hydroxylase-2 mediated inactivation of phosphorylated-Akt to inhibit induced- thrombosis and inflammation -
  Phosphorylation of Akt (pAkt) regulates multiple physiological and pathological processes including thrombosis and inflammation. In an approach to inhibit the pathological signalling of pAkt by prolyl-hydroxylase-2 (PHD2) we employed alpha-ketoglutarate (AKG), a cofactor of PHD2. Octyl-AKG supplementation to platelets promoted PHD2 activity through elevated intracellular AKG:succinate ratio and reduced aggregation in vitro by suppressing pAkt1(Thr308). Augmented PHD2 activity was confirmed by increased hydroxylated-proline alongside enhanced binding of PHD2 to pAkt in AKG-treated platelets. Contrastingly, inhibitors of PHD2 significantly increased pAkt1 in platelets. Octyl-AKG followed similar mechanism in monocytes to inhibit cytokine secretion in vitro. Our data also describe a suppressed pAkt1 and reduced activation of platelet and leukocyte obtained from mice supplemented with dietary-AKG, unaccompanied by alteration in their counts. Dietary-AKG significantly reduced clot formation and leukocyte accumulation in various organs including lung of mice treated with thrombosis-inducing agent carrageenan. Importantly, we observed a significant rescue effect of dietary-AKG on inflamed lung of SARS-CoV-2 infected hamsters. AKG significantly reduced leukocyte accumulation, clot formation and viral load alongside downmodulation of pAkt in lung of the infected animals. Therefore, our study suggests a safe implementation of dietary-AKG in prevention of Akt-driven anomalies including thrombosis and inflammation, highlighting a better pulmonary management in COVID-19.
  🖺 Full Text HTML: Alpha-ketoglutarate augments prolyl hydroxylase-2 mediated inactivation of phosphorylated-Akt to inhibit induced-thrombosis and inflammation
• Mask mandate and use efficacy for COVID-19 containment in US States -

  Background: COVID-19 pandemic mitigation requires evidence-based strategies. Because COVID-19 can spread via respired droplets, most US states mandated mask use in public settings. Randomized control trials have not clearly demonstrated mask efficacy against respiratory viruses, and observational studies conflict on whether mask use predicts lower infection rates. We hypothesized that statewide mask mandates and mask use were associated with lower COVID-19 case growth rates in the United States. Methods: We calculated total COVID-19 case growth and mask use for the continental United States with data from the Centers for Disease Control and Prevention and Institute for Health Metrics and Evaluation. We estimated post-mask mandate case growth in non-mandate states using median issuance dates of neighboring states with mandates. Results: Earlier mask mandates were not associated with lower total cases or lower maximum growth rates. Earlier mandates were weakly associated with lower minimum COVID-19 growth rates. Mask use predicted lower minimum but not lower maximum growth rates. Growth rates and total growth were comparable between US states in the first and last mask use quintiles during the Fall-Winter wave. These observations persisted for both natural logarithmic and fold growth models and when adjusting for differences in US state population density. Conclusions: We did not observe association between mask mandates or use and reduced COVID-19 spread in US states. COVID-19 mitigation requires further research and use of existing efficacious strategies, most notably vaccination.

  🖺 Full Text HTML: Mask mandate and use efficacy for COVID-19 containment in US States
• Learning torus PCA based classification for multiscale RNA backbone structure correction with application to SARS- CoV-2 -
  Reconstructions of structure of biomolecules, for instance via X-ray crystallography or cryo-EM frequently contain clashes of atomic centers. Correction methods are usually based on simulations approximating biophysical chemistry, making them computationally expensive and often not correcting all clashes. We propose a computationally fast data- driven statistical method yielding suites free from within-suite clashes: From such a clash free training data set, devising mode hunting after torus PCA on adaptive cutting average linkage tree clustering (MINTAGE), we learn RNA suite shapes. With classification based on multiscale structure enhancement (CLEAN), for a given clash suite we determine its neighborhood on a mesoscopic scale involving several suites. As corrected suite we propose the Frechet mean on a torus of the largest classes in this neighborhood. We validate CLEAN MINTAGE on a benchmark data set, compare it to a state of the art correction method and apply it, as proof of concept, to two exemplary suites adjacent to helical pieces of the frameshift stimulation element of SARS-CoV-2 which are difficult to reconstruct. In contrast to a recent reconstruction proposing several different structure models, CLEAN MINTAGE unanimously proposes structure corrections within the same clash free class for all suites.
  🖺 Full Text HTML: Learning torus PCA based classification for multiscale RNA backbone structure correction with application to SARS-CoV-2
• RIG-I-induced innate antiviral immunity protects mice from lethal SARS-CoV-2 infection -
  The SARS-CoV-2 pandemic has underscored the need for rapidly employable prophylactic and antiviral treatments against emerging viruses. Nucleic acid agonists of the innate immune system can be administered to activate an effective antiviral program for prophylaxis in exposed populations, a measure of particular relevance for SARS-CoV-2 infection due to its efficient evasion of the host antiviral response. In this study, we utilize the K18-hACE2 mouse model of COVID-19 to examine whether prophylactic activation of the antiviral receptor RIG-I protects mice from SARS-CoV-2 infection. Systemic treatment of mice with a specific RIG-I ligand one to seven days prior to infection with a lethal dose of SARS-CoV-2 improved their survival of by up to 50 %. Improved survival was associated with lower viral load in oropharyngeal swabs and in the lungs and brain of RIG-I-treated mice. Moreover, despite antiviral protection, the surviving mice that were treated with RIG-I ligand developed adaptive SARS-CoV-2-specific immunity. These results reveal that prophylactic RIG-I activation by synthetic RNA oligonucleotides is a promising strategy to convey short-term, unspecific antiviral protection against SARS-CoV-2 infection and may be a suitable broad-spectrum approach to constraining the spread of newly emerging viruses until virus-specific therapies and vaccines become available.

• By Default: How Mothers in Different-Sex Dual-Earner Couples Account for Inequalities in Pandemic Parenting -
  The COVID-19 pandemic dramatically increased families’ childcare responsibilities, disproportionately affecting mothers and undermining their careers and wellbeing. Using two waves of interviews with 77 mothers of young children, we examined why mothers—especially in dual-earner, different-gender couples—took on more pandemic parenting. We found that pre-pandemic gendered structures of paid work led many families to lean on mothers by default. First, within-couple gaps in job types, pay, and work hours led some mothers to do more childcare to protect partners’ work as primary earners. Second, educational gaps within couples led some mothers to do more as the only parent able to work fully remote. Third, pre-pandemic childcare gaps within couples led children (and partners) to rely more heavily on mothers, even when both partners were home full-time. We discuss the implications for research on gender inequalities in paid work and parenting and for policy efforts to address gender inequalities at home.
  🖺 Full Text HTML: By Default: How Mothers in Different-Sex Dual-Earner Couples Account for Inequalities in Pandemic Parenting
• The Inherent Flexibility of Receptor Binding Domains in SARS-CoV-2 Spike Protein -
  Spike (S) protein is the primary antigenic target for neutralization and vaccine development for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It decorates the virus surface and undergoes large conformational changes of its receptor binding domain (RBD) to enter the host cell, as the abundant structural studies suggest. Here, we observe Down, one-Up, one-Open, and two-Up-like structures in enhanced molecular dynamics simulations without pre- defined reaction coordinates. The RBDA transition from Down to one-Up is supported by transient salt-bridges between RBDA and RBDC and by the glycan at N343B. Reduced interactions between RBDA and RBDB induce the RBDB motions toward two- Up. Glycan shielding for neutralizing antibodies is the weakest in one-Open. Cryptic pockets are revealed at the RBD interfaces in intermediate structures between Down and one-Up. The inherent flexibility in S-protein is, thus, essential for the structure transition and shall be considered for antiviral drug rational design or vaccine development.

• Small-molecule ligands can inhibit -1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses -
  Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use -1 programmed ribosomal frameshifting (-1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates -1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored a group of 6 small-molecule ligands, evaluating their activity against the frameshift signals from a panel of representative bat CoVs–the most likely source of future zoonoses–as well as SARS-CoV-2 and MERS-CoV. We found that whereas some ligands had notable activity against only a few of the frameshift signals, the serine protease inhibitor nafamostat suppressed -1 PRF significantly in several of them, while having limited to no effect on -1 PRF caused by frameshift signals from other viruses used as negative controls. These results suggest it is possible to find small- molecule ligands that inhibit -1 PRF specifically in a broad spectrum of CoVs, establishing the frameshift signal as a viable target for developing pan-coronaviral therapeutics.
  🖺 Full Text HTML: Small-molecule ligands can inhibit -1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses
• Covid-19 Associated Hepatitis in children (CAHC) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. -

  Background: Besides Covid-19, SARS-CoV-2 infection has been associated with Multiple Inflammatory Syndrome in children (MIS-C). However, a unique presentation of a transient form of hepatitis in pediatric age group occurring subsequent to the asymptomatic SARS-CoV-2 infection is yet to be reported in children. Presently the clinical presentation, temporal association and characteristics of the cases of CAHC different than MIS-C hepatitis, is being reported. Methods: As a retrospective and follow up observational study we reviewed all pediatric patients presenting with acute hepatitis. We observed a sudden rise of features of hepatitis in a group of pediatric patients during the second wave of SARS CoV-2 infections, where - children or adolescents developing sudden onset acute hepatitis with no history of pre-existing liver disease or familiar etiology of acute hepatitis besides having a COVID-19 RT-PCR positivity within 3-6 weeks or a retrospectively proven Covid-19 infection with high titer SARS CoV-2 antibodies. Such subjects had asymptomatic Covid-19 infection, while in contrast another group of 8 patients having findings suggestive of MIS-C was observed with protracted and grave presentation, with multiple organ involvement along with Covid-19 diagnosis. These patients were negative for conventional Hepatitis A, B, C and E seromarkers but had high titer of SARS CoV-2 antibodies. Results: Among 33 patients who presented with hepatitis, 25 patients had features of CAHC, they had hepatitis only, lacked any typical Covid-19 symptoms, had normal to borderline inflammatory markers, with admission to general care wards, with uneventful recovery on supportive treatment. Whereas remaining 8 patients with MIS-C associated hepatitis required admission to critical care, they had high level of inflammatory markers and 3 (37.5%) had an adverse outcome. Conclusion: With emergence of newer variants of concern including the Delta variant which was responsible for the massive wave of Covid-19 across India, with varied presentations, CAHC is one of them. Such new entities need to be timely identified and differentiated from other types of emerging syndromes in children for appropriate management.

  🖺 Full Text HTML: Covid-19 Associated Hepatitis in children (CAHC) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.
• Effect of an Ayurvedic intervention (Ayush-64) in mild to moderate COVID-19: An exploratory prospective single arm clinical trial -
  Background: Ayush-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences (CCRAS). In the present study, we repurposed it for use in mild to moderate COVID-19 cases based on a pilot study against Influenza like illness (ILI) and molecular docking study which revealed that several compounds isolated from Ayush-64 demostrated antiviral activity. Purpose: To evaluate the role of Ayush-64 in clinical recovery of mild to moderate COVID-19 pattients Study Design: A single arm, pilot study in mild to moderate COVID-19 patients Methods: The study was conducted from 20th June, 2020 to 11th August, 2020 at Chaudhary Brahm Prakash Ayurved Charak Sansthan (CBPACS), New Delhi, India involving 37 confirmed COVID-19 participants. Ayush 64 tablets in the dose of two tablets (500 mg each) thrice daily was given to the participants for a duration of either 8 or 14 days. Number of participants showing ‘clinical recovery’ was set as primary outcome. Percentage of participants with negative SARS-CoV-2 on nasal or throat swab in a 2-day consecutive real time RT-PCR test was evaluated as secondary outcome. Result: In the study 86.1% participants have shown clinical recovery after 14 days intervention of Ayush-64, out of which 75% clinically recovered within 7 days. Finding of RT-PCR test has shown that 69.4% participants turned negative till 15th day, out of which 50% became negative on 8th day. No AE/ ADR was observed during the course of the study. Conclusion: Ayush-64 is a safe treatment option in mild to moderate COVID-19 cases and is likely to significantly facilitate clinical improvement in terms of duration for clinical recovery and attaining negative conversion, without any ADR/AE.
  🖺 Full Text HTML: Effect of an Ayurvedic intervention (Ayush-64) in mild to moderate COVID-19: An exploratory prospective single arm clinical trial
• Quantitative SARS-CoV-2 tracking of variants Delta, Delta plus, Kappa and Beta in wastewater by allele-specific RT- qPCR -

  The Delta (B.1.617.2) variant has caused major devastation in India and other countries around the world. First detected in October 2020, it has now spread to more than 100 countries, prompting WHO to declare it as a global variant of concern (VOC). The Delta (B.1.617.2), Delta plus (B.1.617.2.1) and Kappa (B.1.617.1) variants are all sub-lineages of the original B.1.617 variant. Prior to the inception of B.1.617, vaccine rollout, safe-distancing and timely lockdowns greatly reduced COVID-19 hospitalizations and deaths. However, the Delta variant, allegedly more infectious and for which existing vaccines seemed less effective, has catalyzed the resurgence of cases. Therefore, there is an imperative need for increased surveillance of the B.1.617 variants. Efforts have been made to utilize wastewater-based surveillance for community-based tracking of SARS-CoV-2 variants, however wastewater with its low SARS-CoV-2 viral titers and mixtures of viral variants, requires assays to be variant-specific yet accurately quantitative for meaningful interpretation. Following on the design principles of our previous assays for the Alpha variant, here we report allele- specific RT-qPCR assays targeting mutations T19R, D80A, K417N, T478K and E484Q, for quantitative detection and discrimination of the Delta, Delta plus, Kappa and Beta variants in wastewater. This method is open-sourced and can be implemented using commercially available RT-qPCR protocols, and would be an important tool for tracking the spread of B.1.617 and the Beta variants in communities.

  🖺 Full Text HTML: Quantitative SARS-CoV-2 tracking of variants Delta, Delta plus, Kappa and Beta in wastewater by allele-specific RT-qPCR
• Development and performance evaluation of a low-cost in-house rRT-PCR assay in Ecuador for the detection of SARS- CoV-2 -

  Antecedents: Ecuador has had the greatest fatality rate from Coronavirus (COVID-19) in South America during the SARS-CoV-2 pandemic. To control the pandemic, it is necessary to test as much population as possible to prevent the spread of the SARS-CoV-2 infection. For the Ecuadorian population, accessing a PCR test is challenging, since commercial screening kits tend to be expensive. Objective: the objective of this study was to develop an in-house duplex rRT-PCR protocol for the detection of SARS-CoV-2 that contributes to the screening while keeping quality and low testing costs. Results: An in-house duplex rRT-PCR protocol based on the viral envelope (E) gene target of SARS-CoV-2 and a human ribonuclease P gene (RP) as an internal control is reported. The protocol was optimized to obtain primers E with an efficiency of up to 94.45% and detection of 100% of SARS-CoV-2 up to 15 copies per uL. The clinical performance was determined by a sensibility of 93.8% and specificity of 98.3%. Conclusion: we developed, standardized, and validated a low-cost, sensitive in-house duplex rRT-PCR assay that may be utilized in low-income countries.

  🖺 Full Text HTML: Development and performance evaluation of a low-cost in-house rRT-PCR assay in Ecuador for the detection of SARS-CoV-2
• Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): study protocol for a multicenter randomized controlled trial -

  Introduction Noninvasive ventilation delivered by helmet is has been used for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. The aim of this study is to compare helmet noninvasive ventilation with usual care versus usual care alone to reduce the mortality. Methods and analysis This is a multicenter, pragmatic, parallel, randomized controlled trial that compares helmet noninvasive ventilation with usual care to usual care alone in 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness. Ethics and dissemination Approvals are obtained from the Institutional Review Boards (IRBs) of each participating institution. Our findings will be published in peer-review journals and presented at relevant conferences and meetings.

  🖺 Full Text HTML: Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): study protocol for a multicenter randomized controlled trial
• Data-driven Testing Program Improves Detection of COVID-19 Cases and Reduces Community Transmission -

  COVID-19 remains a global threat in the face of emerging SARS-CoV-2 variants and gaps in vaccine administration and availability, and organizations must be prepared to detect and mitigate its risk to their people and activities. In this report we share key lessons learned from an adaptive COVID-19 testing program implemented at a mid-sized university in the Midwest. The program utilized two simple, diverse, and easily interpretable machine learning models to quickly and accurately predict which students were at elevated risk for contracting COVID-19 and should be called proactively for testing. Our adaptive testing cohorts produced positivity rates that were 26% higher than the random cohort: 0.58% positivity (95% CI 0.47% to 0.68%) from 19,171 tests, and 0.46% positivity (95% CI 0.41% to 0.51%) from 64,003 tests, respectively. Within 14 days of their selection, 2.94% of the adaptive cohort tested positive, compared to 1.27% of the random cohort. Close contacts who were predicted by the adaptive testing models received a COVID-19 test within an average of 0.94 days (95% CI 0.78 to 1.11) of the source testing positive, while those who were manually contact traced were tested in an average of 1.92 days (95% CI 1.81 to 2.02). These results suggest that machine learning strategies can improve surveillance testing effectiveness, especially in a university setting, by effectively distributing testing resources and potentially reducing community transmission.

  🖺 Full Text HTML: Data-driven Testing Program Improves Detection of COVID-19 Cases and Reduces Community Transmission
• Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases -

  Objective To describe the characteristics of COVID-19 vaccine breakthrough infections among systemic autoimmune rheumatic disease (SARD) patients. Methods We identified SARDs patients in a large healthcare system with COVID-19 vaccination at least 14 days prior to a positive SARS-CoV-2 molecular test. Details of the SARD diagnosis, vaccination status, and COVID-19 infection were extracted. Results Of 340 confirmed COVID-19 infections among SARDs patients between December 11th, 2020 (date of first COVID-19 vaccine approval in the US) and July 30th, 2021, we identified 16 breakthrough infections. Seven (44%) received the Pfizer-BioNtech vaccine, five (31%) received the Moderna vaccine, and four (25%) received the Janssen/Johnson & Johnson vaccine. The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myopathy (3, 19%), and systemic lupus erythematosus (3, 19%). Rituximab (5, 31%), glucocorticoids (4, 25%), and mycophenolate mofetil (4, 25%) were the most frequent treatments. Among the breakthrough infections, 15 (93%) were symptomatic, six (38%) were hospitalized, one (6%) required mechanical ventilation, and two (13%) died. Conclusions Symptomatic, including severe, breakthrough infections were observed in SARDs patients; many were on treatments associated with attenuated antibody responses to vaccination. Further studies are needed to determine the rate of breakthrough infection associated with SARD treatments and other features.

  🖺 Full Text HTML: Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases
• Adverse events following COVID-19 virus vaccination in Japanese young population: The first cross-sectional study conducted by a questionnaire survey after the first-time-injection -

  A cross-sectional study was conducted to clarify the adverse events of COVID-19 vaccines in Japanese young population. The proportion of participants with adverse events at the vaccination site (immediately or within 30 minutes after vaccination) was 0.5%, and anaphylaxis occurred in one female student (0.03%). We analyzed 1,877 data obtained from a questionnaire survey of 1,993 vaccinated individuals. Eighty-two percent of participants complained of local adverse events. Injection site pain was the most common local adverse event (71%). Systemic adverse events occurred in 48% of participants. The most common adverse event was myalgia (34%). A multivariable logistic regression model was used to determine risk factors. Local adverse events were associated with sex (female) and allergy history, with odds ratios (ORs) (95% confidence interval [CI]) of 2.15 (1.69-2.73) and 1.73 (1.10-2.74), respectively. Systemic adverse events were associated with sex (female), age (<20 years old), allergy history, and history of adverse events with previous medications, with ORs (95% CI) of 2.49 (2.03-3.06), 1.80 (1.44-2.24), 1.39 (1.03-1.89), and 1.53 (1.02-2.29). The results of this study clarified for the first time that age less than 20 years is a risk factor for systemic adverse events from the COVID-19 Vaccine Moderna Intramuscular Injection. This information will give impacts on considering adverse events and its mechanisms in mRNA vaccination.

  🖺 Full Text HTML: Adverse events following COVID-19 virus vaccination in Japanese young population: The first cross-sectional study conducted by a questionnaire survey after the first-time-injection

From Clinical Trials

• Echinacea Drug for Covid-19 - Condition:   Covid19
  Intervention:   Drug: ECHINACEA ARKOPHARMA
  Sponsors:  
  Jesús R. Requena;   IDIS;   SALUD;   Laboratoires Arkopharma
  Recruiting

• Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise - Condition:   Covid19
  Interventions:   Biological: COVI-MSC;   Biological: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment - Condition:   Covid19
  Interventions:   Drug: Hydroxychloroquine;   Drug: Favipiravir;   Drug: Favipiravir + Hydroxychloroquine;   Drug: Placebo
  Sponsor:   Health Institutes of Turkey
  Completed

• SOLIDARITY Finland Long COVID-19 - Condition:   Covid19
  Intervention:   Drug: Remdesivir
  Sponsors:  
  Clinical Urology and Epidemiology Working Group;   University of Helsinki;   World Health Organization;   Helsinki University Central Hospital;   Hyvinkää Hospital;   Kanta-Häme Central Hospital;   Kuopio University Hospital;   Oulu University Hospital;   Porvoo Hospital;   Seinajoki Central Hospital;   Mikkeli Central Hospital;   Tampere University Hospital
  Recruiting

• ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Danicopan;   Other: Placebo;   Drug: Remdesivir
  Sponsor:   National Institute of Allergy and Infectious Diseases (NIAID)
  Recruiting

• Project FLUx COntact-CoVID-19 Faculty of Medicine Paris-Saclay - Condition:   Covid19
  Interventions:   Other: Antigenic tests (on saliva samples);   Other: Individual electronic sensor port;   Other: Atmospheric measurements of CO2
  Sponsor:  
  Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose) - Condition:   COVID-19 Lower Respiratory Infection
  Interventions:   Biological: AG0302-COVID19 for Intramuscular Injection;   Biological: AG0302-COVID19 for Intradermal Injection
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Not yet recruiting

• Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Drug: Potassium Canrenoate
  Sponsors:   Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico;   University of Milan;   IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Not yet recruiting

• COVID-19 Administration of Single-Dose Subcutaneous or Intramuscular Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition:   COVID-19
  Intervention:   Drug: casirivimab and imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Reactogenicity, Safety, and Immunogenicity of Covid-19 Vaccine Booster - Condition:   Covid19
  Interventions:   Biological: Placebo;   Biological: Inactivated vaccine booster;   Biological: mRNA vaccine booster;   Drug: Viral vector vaccine booster
  Sponsors:   Universidad del Desarrollo;   Ministry of Health, Chile;   University of Chile;   Pontificia Universidad Catolica de Chile
  Active, not recruiting

• The Efficacy of Nigella Sativa Versus VitaminD3 as Supplement Therapy in Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Intervention:   Dietary Supplement: Nigella Sativa capsule twice daily
  Sponsor:   Ain Shams University
  Recruiting

• Efficacy, Immunogenicity and Safety of COVID-19 Vaccine , Inactivated in Children and Adolescents - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: Controlled vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Recruiting

• Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With Quadrivalent Influenza Vaccine And 23-valent Pneumococcal Polysaccharide Vaccine - Condition:   COVID-19
  Interventions:   Biological: Experimental Group1;   Biological: Experimental Group 2;   Biological: Experimental Group 3
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Study to Evaluate the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schemes in an Elderly Population - Condition:   COVID-19 Vaccines
  Intervention:   Drug: Gam-COVID-Vac / Gam-COVID-Vac
  Sponsor:   Ministerio de Salud de Ciudad Autónoma de Buenos Aires
  Recruiting

• Collaborative Study to Evaluate Heterologous Vaccination Against Covid-19 in Aargentina - Conditions:   COVID-19 VACCINE;   Covid19
  Intervention:   Biological: COVID-19 vaccines
  Sponsor:   Ministry of Public Health, Argentina
  Not yet recruiting

From PubMed

• Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19 - Current standard treatment of COVID-19 lacks in effective antiviral options. Plitidepsin, a cyclic depsipeptide authorized in Australia for patients with refractory multiple myeloma, has recently emerged as a candidate anti-SARS- CoV-2 agent. The aim of this review was to summarize current knowledge on plitidepsin’s clinical profile, anti-tumour and anti-SARS-CoV-2 mechanisms and correlate this with available or anticipated, preclinical or clinical evidence on the drug’s potential for COVID-19…

• Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition - The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (M^(pro)) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for…

• Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib - Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition…

• Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays - In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)-two natural stilbene polyphenols with manifold, well known biological activities-with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking…

• Efficiency of pooled surveillance testing in academic labs to detect and inhibit COVID-19 outbreaks - Robust surveillance testing is a key strategic plan to prevent COVID-19 outbreaks and slow the spread of the SARS-CoV-2 pandemic; however, limited resources, facilities and time often impair the implementation of a widespread surveillance effort. To mitigate these resource limitations, we employed a strategy of pooling samples, reducing reagent cost and processing time. Through utilizing academic faculty and labs, successful pooled surveillance testing was conducted throughout Fall 2020 semester…

• Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity - Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve…

• Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19 - The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA- approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus’ pathogenic mechanism and support current therapeutic strategies. We show…

• Assessing the potential correlation of polymorphisms in the IL6R with relative IL6 elevation in severely ill COVID-19 patients’ - CONCLUSIONS: While it is unlikely that “cytokine storm” is the norm in severe COVID19, baseline elevations above 150 pg/ml may be associated with worst outcomes and as such may warrant treatment considerations. So far no clinical studies used IL-6 baseline assessment to stratify the patient population participating in clinical studies. We believe that careful examination and interpretation of the IL-6 levels and genetic variants can help to determine a patient population with a potentially very…

• Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations - Bioactive peptides derived from food proteins are becoming increasingly popular due to the growing awareness of their health-promoting properties. The structure and mechanism of anti-cancer action of pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) derived from a rice bran protein are not known. Theoretical and experimental methods were employed to fill this gap. The conformation analysis of the EQRPR pentapeptide was performed first and the obtained lowest energy conformer was optimized. The…

• BTK inhibitors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A systematic review - CONCLUSIONS AND RELEVANCE: BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration.

• NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain - The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) contains two active sites that catalyze nucleotidyl-monophosphate transfer (NMPylation). Mechanistic studies and drug discovery have focused on RNA synthesis by the highly conserved RdRp. The second active site, which resides in a Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain, is poorly characterized, but both catalytic reactions are essential for viral replication. One study showed that NiRAN transfers…

• Aromatic Cadinane Sesquiterpenoids from the Fruiting Bodies of Phellinus pini Block SARS-CoV-2 Spike-ACE2 Interaction - The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (1-4), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic…

• SARS-CoV-2 host cell entry: an in silico investigation of potential inhibitory roles of terpenoids - CONCLUSION: The identified terpenoids from this study provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell-mediated entry proteins. They are therefore recommended for further in vitro and in vivo studies towards developing entry inhibitors against the ongoing COVID-19 pandemic.

• Host ADP-ribosylation and the SARS-CoV-2 macrodomain - The COVID-19 pandemic has prompted intense research efforts into elucidating mechanisms of coronavirus pathogenesis and to propose antiviral interventions. The interferon (IFN) response is the main antiviral component of human innate immunity and is actively suppressed by several non-structural SARS-CoV-2 proteins, allowing viral replication within human cells. Differences in IFN signalling efficiency and timing have emerged as central determinants of the variability of COVID-19 disease severity…

• COVID-19 Ocular Prophylaxis: The Potential Role of Ozonated-Oils in Liposome Eyedrop Gel - CONCLUSIONS: SARS-CoV-2 transmission through the ocular surface should not be ignored. Although the prevalence of coronavirus disease 2019 conjunctivitis infection is low, the need for a barrier to prevent possible viral infection is warranted. OED treatment may prevent the risk of SARS-CoV-2 infection after 72 hours of twice-daily applications.

From Patent Search

• Camellia nitidissima C.W.Chi Caffeine and Chlorogenic acid composition for anti-SARS-CoV-2 and preparation method and application thereof - - link

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

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

• Mascarilla impermeable - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B.1.525尼日利亚突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.525尼日利亚突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link