Covid-19 Sentry

Contents

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

From Preprints

• Evaluation of COVID-19 as a risk factor for maternal-fetal and neonatal complications: protocol of a systematic review and meta-analysis of cohort and case-control studies. -

  Background: COVID-19 in pregnant women has been suggested to impair maternal-fetal and neonatal outcomes. We then designed the present systematic review with meta-analysis to evaluate the repercussion of such disease over maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery, birth weight, Apgar score, presence of intrauterine growth restriction (IGR), and presence of amniotic fluid change. Methods: We will conduct a computerized search through MEDLINE/PubMed, LILACS/BIREME, Web of science, Biorxiv, Medrxiv, and Embase on July 23, 2020. We will include cohort and case-control studies fully reported comparing pregnant women with COVID-19 with those not affected by the disease for maternal fetal and neonatal mortality, need for intensive care, way of delivery, premature delivery occurrence, birth weight, Apgar scores, presence of intrauterine growth restriction, and presence of amniotic fluid change. Three doubles of reviewers will perform in duplicate and independently all steps on screening, risk of bias judgments, and data extraction with ability to discuss disagreements with supervising authors. Pooled effects will be estimated by both fixed and random-effects models and presented according to qualitative and quantitative heterogeneity assessment. Sensitivity analyses will be performed as well as a priori subgroup, meta-regression and multiple meta-regression analyses. We will also evaluate the risk of selective publication by assessing funnel plot asymmetry and the quality of the evidence by the application of the GRADE recommendations. Discussion: This systematic review with meta-analysis aims to assess the repercussion of COVID-19 in pregnant women over maternal-fetal and neonatal outcomes and to help clinicians and health systems improve such population outcomes throughout the current pandemic. Systematic review registration: This review protocol was also submitted to PROSPERO registration on February 9, 2021.

  🖺 Full Text HTML: Evaluation of COVID-19 as a risk factor for maternal-fetal and neonatal complications: protocol of a systematic review and meta-analysis of cohort and case-control studies.
• Clinical evaluation of the molecular-based BD SARS-CoV-2/Flu for the BD MAX™ System -

  Efficient and accurate assays for the differential diagnosis of COVID-19 and/or influenza (flu) could facilitate optimal treatment for both diseases. Diagnostic performance related to SARS-CoV-2 and Flu A/B detection was characterized for the BD SARS-CoV-2/Flu for BD MAX™ System (MAX SARS-CoV-2/Flu) multiplex assay in comparison with BD BioGx SARS-CoV-2 Reagents for BD MAX™ System (BioGx SARS-CoV-2) and the Cepheid Xpert® Xpress Flu/RSV (Xpert Flu). Two hundred and thirty-five nasopharyngeal specimens were obtained from external vendors. MAX SARS-CoV-2/Flu had positive percent agreement (PPA) and negative percent agreement (NPA) values for SARS-CoV-2 and Flu A/B that met FDA-EUA acceptance criteria of >95%.

  🖺 Full Text HTML: Clinical evaluation of the molecular-based BD SARS-CoV-2/Flu for the BD MAX™ System
• Vaccine Rollout Strategies: The Case for Vaccinating Essential Workers Early -

  In planning for upcoming mass vaccinations against COVID-19, many jurisdictions have proposed using primarily age-based rollout strategies, where the oldest are vaccinated first and the youngest last. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection (and hence transmission of SARS-CoV-2), we propose that such age-based rollouts are both less equitable and less effective than strategies that prioritize essential workers. We demonstrate using modelling that strategies that target essential workers earlier consistently outperform those that do not, and that prioritizing essential workers provides a significant level of indirect protection for older adults. This conclusion holds across numerous outcomes, including cases, hospitalizations, deaths, prevalence of Long COVID, chronic impacts of COVID, quality adjusted life years lost and net monetary benefit lost. It also holds over a range of possible values for the efficacy of vaccination against infection. Our analysis focuses on regimes where the pandemic continues to be controlled with distancing and other measures as vaccination proceeds, and where the vaccination strategy is expected to last for over the coming 6-8 months - for example British Columbia, Canada. In such a setting with a total population of 5M, vaccinating essential workers sooner is expected to prevent over 200,000 infections, over 600 deaths, and to produce a net monetary benefit of over $500M. 20-25% of the quality adjusted life years lost, and 28-34% of the net monetary benefit lost, are due to chronic impacts of COVID-19.

  🖺 Full Text HTML: Vaccine Rollout Strategies: The Case for Vaccinating Essential Workers Early
• Comparison of the clinical characteristics and mortality in ARDS due to COVID-19 versus ARDS due to Influenza A-H1N1pdm09 -

  Abstract Importance: Infection with the SARS-Cov-2 and Influenza A-H1N1 viruses is responsible for the first pandemics of the 21st century. Both of these viruses can cause severe pneumonia and acute respiratory distress syndrome (ARDS). The clinical differences and mortality associated with these two pandemic pneumonias in patients with ARDS are not well established Objective: To compare case-fatality between ARDS-Covid-19 and ARDS-Influenza A (H1N1), adjusting for known prognostic risk factors. Design, Setting and Participants: One hundred forty-seven patients with COVID-19 were compared with 94 with Influenza A-H1N1, all of these were admitted to the intensive care unit of the Referral Center for Respiratory Diseases and COVID-19 in Mexico City and fulfilled the criteria of ARDS. Results: Patients arrived at the hospital after 9 days of symptoms. Influenza patients had more obesity, more use of Norepinephrine, and higher levels of lactic dehydrogenase and glucose, and fewer platelets and lower PaO2/FIO2. Crude mortality was higher in COVID than in influenza (39% vs. 22%; p = 0.005). In a Cox proportional hazard model, patients with a diagnosis of COVID-19 had a hazard ratio (HR) = 3.7; 95% Confidence Interval [CI] = 1.9-7.4, adjusted for age, gender, sequential organ failure assessment (SOFA) score, ventilatory ratio, and prone ventilation. In the fully adjusted model, the ventilatory ratio and the absence of prone-position ventilation were also predictors of mortality. CONCLUSION: COVID-19 patients treated in an intensive care unit (ICU) had a 3.7 times higher risk of death than similar patients with Influenza A-H1N1, after adjusting for SOFA score and other relevant risk factors for mortality.

  🖺 Full Text HTML: Comparison of the clinical characteristics and mortality in ARDS due to COVID-19 versus ARDS due to Influenza A-H1N1pdm09
• The differential impact of the COVID-19 epidemic on Medicaid expansion and non-expansion states -

  Medicaid expansion is a federally-funded program to expand health care access and coverage to economically challenged populations by increasing eligibility to Medicaid enrollment and investing in public health preventive services in the individual states. Yet, when the COVID-19 epidemic plagued the country, fourteen states were practicing their chosen decision not to enact the Medicaid expansion policy. We examined the consequences of this nationwide split in Medicaid design on the spread of the COVID-19 epidemic between the expansion and non-expansion states. Our study shows that, on average, the expansion states had 217.56 fewer confirmed COVID-19 cases per 100,000 residents than the non-expansion states [-210.41; 95%CI (-411.131) - (-2.05); P<0.05]. Also, the doubling time of COVID-19 cases in Medicaid expansion states was longer than that of non-expansion states by an average of 1.68 days [1.6826; 95%CI 0.4035-2.9617; P<0.05]. These findings suggest that proactive investment in public health preparedness was an effective protective policy measure in this crisis, unsurpassed by the benefits of COVID-19 emergency plans and funds. The study findings could be relevant to policymakers and healthcare strategists in non-expansion states considering their states9 preparations for such public health crises.

  🖺 Full Text HTML: The differential impact of the COVID-19 epidemic on Medicaid expansion and non-expansion states
• A Comprehensive County Level Framework to Identify Factors Affecting Hospital Capacity and Predict Future Hospital Demand -

  Background: As of February 19, 2021, our review yielded a small number of studies that investigated high resolution hospitalization demand data from a public health planning perspective. The earlier studies compiled were conducted early in the pandemic and do not include any analysis of the hospitalization trends in the last 3 months when the US experienced a substantial surge in hospitalization and ICU demand. The earlier studies also focused on COVID 19 transmission influence on COVID 19 hospitalization rates. While this emphasis is understandable, there is evidence to suggest that non COVID hospitalization demand is being displaced due to the hospitalization and ICU surge. Further, with the discovery of multiple mutated variants of COVID 19, it is important to remain vigilant in an effort to control the pandemic. Given these circumstances, the development of a high resolution framework that examines overall hospitalizations and ICU usage rate for COVID and non COVID patients would allow us to build a prediction system that can identify potential vulnerable locations for hospitalization capacity in the nation so that appropriate remedial measures can be planned. Method: The current study recognizes that COVID 19 has affected overall hospitalizations, not only COVID 19 hospitalizations. Drawing from the recently released Department of Health and Human services (DHH) weekly hospitalization data (or the time period August 28th , 2020 to January 22nd, 2021.), we study the overall hospitalization and ICU usage as two components: COVID 19 hospitalization and ICU per capita rates; and non COVID hospitalization and ICU per capita rates. A mixed linear mixed model is adopted to study the response variables in our study. The estimated models are subsequently employed to generate predictions for county level hospitalization and ICU usage rates in the future under a host of COVID 19 transmission scenarios considering the new variants of COVID 19 and vaccination impacts. Findings: We find a significant association of the virus transmissibility with COVID (positive) and non COVID (negative) hospitalization and ICU usage rates. Several county level factors including demographics, mobility and health indicators are also found to be strongly associated with the overall hospitalization and ICU demand. Among the various scenarios considered, the results indicate a small possibility of a new wave of infections that can substantially overload hospitalization and ICU usage. In the scenario where vaccinations proceed as expected reducing transmission, our results indicate that hospitalizations and ICU usage rates are likely to reduce significantly. Interpretation: The research exercise presents a framework to predict evolving hospitalization and ICU usage trends in response to COVID 19 transmission rates while controlling for other factors. Our work highlights how future hospitalization demand varies by location and time in response to a range of pessimistic and optimistic scenarios. Further, the exercise allows us to identify vulnerable counties and regions under stress with high hospitalization and ICU rates that can be assisted with remedial measures. The model will also allow hospitals to understand evolving displaced non COVID hospital demand.

  🖺 Full Text HTML: A Comprehensive County Level Framework to Identify Factors Affecting Hospital Capacity and Predict Future Hospital Demand
• Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings -

  Background: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods. Methods: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both standard polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into either viral transport media or an RNA stabilization agent. Quantitative SARS-CoV-2 viral detection by RT-qPCR was compared to that obtained by nasopharyngeal sampling as the reference standard. Pooling specimens in the lab versus pooling swabs at the point of collection was also evaluated. Results: Among 275 participants, flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), mostly missing those with low viral load (<10^3 viral copies/uL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into an RNA stabilizer, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. Pooling sample specimens or swabs both successfully detected samples >10² viral copies/uL. Conclusions: Nasal swabs are likely adequate for clinical diagnosis of acute infections to help expand testing capacity in resource-constrained settings. When collected into an RNA preservative that also inactivates infectious virus, nasal swabs yielded quantitative viral loads approximating those obtained by nasopharyngeal sampling.

  🖺 Full Text HTML: Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings
• A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York -

  Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

  🖺 Full Text HTML: A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York
• Household secondary attack rate of COVID-19 by household size and index case characteristics -

  In this population-wide study in Ontario, Canada, we investigated the household secondary attack rate (SAR) to understand its relationship to household size and index case characteristics. We identified all patients with confirmed COVID-19 between July 1 and November 30, 2020. Cases within households were matched based on reported residential address; households were grouped based on the number of household contacts. The majority of households (68.2%) had a SAR of 0%, while 3,442 (11.7%) households had a SAR ≥75%. Overall household SAR was 19.5% and was similar across household sizes, but varied across index case characteristics. Households where index cases had longer delays between symptom onset and test seeking, households with older index cases, households with symptomatic index cases, and larger households located in diverse neighborhoods, were associated with greater household SAR. Our findings present characteristics associated with greater household SARs and proposes immediate testing as a method to reduce household transmission and incidence of COVID-19.

  🖺 Full Text HTML: Household secondary attack rate of COVID-19 by household size and index case characteristics
• The immunophilin protein FKBPL and its peptide derivatives are novel regulators of vascular integrity and inflammation via NF-kappaB signaling -
  A breakdown in vascular integrity and excessive inflammation are hallmarks of serious pathological conditions including sepsis, acute respiratory distress syndrome (ARDs) and most recently, severe COVID-19. FK506 binding protein like (FKBPL) is a member of the immunophilin protein superfamily with potent anti tumor activity through inhibition of angiogenesis and cancer stemness. An FKBPL based 23mer peptide, ALM201, displayed a good safety and pharmacokinetic profile in a Phase 1a oncology clinical trial and was subsequently designated orphan drug status by the FDA in ovarian cancer. Here we describe a novel role for FKBPL and its peptides in regulating vascular integrity and cytokine production though modulating NFkappaB signaling. FKBPL knockdown promoted endothelial cell barrier permeability, which was further exacerbated upon stimulation with lipopolysaccharide (LPS) and accompanied by increased expression of TNF mRNA and phosphorylation of p65(RelA). Whilst treatment with the FKBPL based pre-clinical peptide, AD-01, increased VE-cadherin endothelial tight junctions following LPS stimulation. Bone marrow derived macrophages (BMDM) from FKBPL haploinsufficient mice (Fkbpl+/-) also demonstrated increased phosphorylation of p65(RelA) in response to LPS stimulation compared to wild-type mice. Furthermore, treatment with AD-01 inhibited p65(RelA) phosphorylation following LPS stimulation resulting in reduced NFkappaB target gene expression and proinflammatory cytokine production. In an in vivo LPS survival model, Fkbpl+/- mice have reduced survival compared to wild-type mice. Moreover, treatment of wild-type mice with the clinical FKBPL-based peptide, ALM201, following LPS injection resulted in a 100% survival rate in mice at experimental endpoint, as well as an abrogation of production of proinflammatory cytokines, TNF and IL-6, in peritoneal lavage washings. Analysis of human genetic biobanks found an association between common genetic variants associated with FKBPL and traits associated with inflammatory disorders such as psoriasis, rheumatoid arthritis and high lymphocyte count. In summary, for the first time, we describe a novel role for FKBPL as a regulator of inflammation and vascular integrity through modulating NFkappaB signaling and FKBPL based therapies demonstrate potent anti inflammatory activity.
  🖺 Full Text HTML: The immunophilin protein FKBPL and its peptide derivatives are novel regulators of vascular integrity and inflammation via NF-kappaB signaling
• Connected Despite Lockdown: The Role of Social Interactions and Social Media Use in Wellbeing -
  Humans are social beings, but during the COVID-19 pandemic, people around the world are periodically in lockdown and are required to try to physically distance themselves from others. The resultant limitation of face-to-face interactions presents a challenge to wellbeing. During periods of lockdown, people can, however, still connect to others via technology, but it is unknown whether such interactions offer benefits comparable to face-to-face interactions. In the present study, we examined how different ways of interacting with others impacted wellbeing during a period of lockdown in the United Kingdom. In a 30-day diary study conducted in April-June 2020, 110 adults reported the time they spent daily on face-to-face interactions and technology-mediated communication (video, phone, text) with different interaction partners. They also indicated the time they spent on active and passive social media use and their end-of-day wellbeing. Multilevel regressions indicated that more face-to-face interactions both within and outside of one’s household positively predicted wellbeing, while technology-mediated communication had less consistent positive effects. Additionally, more active and less passive social media use predicted better wellbeing. These results highlight the complexity of benefits of different kinds of social interactions during lockdown in the COVID-19 pandemic and point to the importance of taking into account communication channels, interaction partners, and how people use social media when studying the effects of connecting to others.
  🖺 Full Text HTML: Connected Despite Lockdown: The Role of Social Interactions and Social Media Use in Wellbeing
• SARS-CoV-2 detection and genomic sequencing from hospital surface samples collected at UC Davis -

  Rationale: There is little doubt that aerosols play a major role in the transmission of SARS-CoV-2. The significance of the presence and infectivity of this virus on environmental surfaces, especially in a hospital setting, remains less clear. Objectives: We aimed to analyze surface swabs for SARS-CoV-2 RNA and infectivity, and to determine their suitability for sequence analysis. Methods: Samples were collected during two waves of COVID-19 at the University of California, Davis Medical Center, in COVID-19 patient serving and staff congregation areas. qRT-PCR positive samples were investigated in Vero cell cultures for cytopathic effects and phylogenetically assessed by whole genome sequencing. Measurements and Main Results: Improved cleaning and patient management practices between April and August 2020 were associated with a substantial reduction of SARS-CoV-2 qRT-PCR positivity (from 11% to 2%) in hospital surface samples. Even though we recovered near-complete genome sequences in some, none of the positive samples (11 of 224 total) caused cytopathic effects in cultured cells suggesting this nucleic acid was either not associated with intact virions, or they were present in insufficient numbers for infectivity. Phylogenetic analysis suggested that the SARS-CoV-2 genomes of the positive samples were derived from hospitalized patients. Genomic sequences isolated from qRT-PCR negative samples indicate a superior sensitivity of viral detection by sequencing. Conclusions: This study confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces contains infectious virus, disputing the importance of fomites in COVID-19 transmission. Ours is the first report on recovering near-complete SARS-CoV-2 genome sequences directly from environmental surface swabs.

  🖺 Full Text HTML: SARS-CoV-2 detection and genomic sequencing from hospital surface samples collected at UC Davis
• Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity -
  Viruses hijack host metabolic pathways for their replicative advantage. Several observational trans-omics analyses associated carbon and amino acid metabolism in coronavirus disease 2019 (COVID-19) severity in patients but lacked mechanistic insights. In this study, using patient-derived multi-omics data and in vitro infection assays, we aimed to understand i) role of key metabolic pathways in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reproduction and ii) its association with disease severity. Our data suggests that monocytes are key to the altered immune response during COVID-19. COVID-19 infection was associated with increased plasma glutamate levels, while glucose and mannose levels were determinants of the disease severity. Monocytes showed altered expression pattern of carbohydrate and amino acid transporters, GLUT1 and xCT respectively in severe COVID-19. Furthermore, lung epithelial cells (Calu-3) showed a strong acute metabolic adaptation following infection in vitro by modulating central carbon metabolism. We found that glycolysis and glutaminolysis are essential for virus replication and blocking these metabolic pathways caused significant reduction in virus production. Taken together, our study highlights that the virus utilizes and re-wires pathways governing central carbon metabolism leading to metabolic toxicity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.
  🖺 Full Text HTML: Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity
• Development of Tribo-Electroceutical Fabrics for Potential Application in Self-sanitizing Personal Protective Equipment (PPE) -
  Attachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm x 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 micro-Watt output power, which is capable of charging a capacitor up to 65 V in only ~50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19.
  🖺 Full Text HTML: Development of Tribo-Electroceutical Fabrics for Potential Application in Self-sanitizing Personal Protective Equipment (PPE)
• SARS-CoV-2 ORF6 disturbs nucleocytoplasmic trafficking to advance the viral replication -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease 2019 pandemic. ORF6 is known to antagonize the interferon signaling by inhibiting the nuclear translocation of STAT1. Here we show that ORF6 acts as a virulence factor through two distinct strategies. First, ORF6 directly interacts with STAT1 in an IFN-independent manner to inhibit its nuclear translocation. Second, ORF6 directly binds to importin 1, which is a nuclear transport factor encoded by KPNA2, leading to a significant suppression of importin 1-mediated nuclear transport. Furthermore, we found that KPNA2 knockout enhances the viral replication, suggesting that importin 1 suppresses the viral propagation. Additionally, the analyses of gene expression data revealed that importin 1 levels decreased significantly in the lungs of older individuals. Taken together, SARS-CoV-2 ORF6 disrupts the nucleocytoplasmic trafficking to accelerate the viral replication, resulting in the disease progression, especially in older individuals.
  🖺 Full Text HTML: SARS-CoV-2 ORF6 disturbs nucleocytoplasmic trafficking to advance the viral replication

From Clinical Trials

• Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Hospitalized Adults With COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVI-AMG;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Safety & Efficacy of Low Dose Aspirin / Ivermectin Combination Therapy for Treatment of Covid-19 Patients - Condition:   Covid19
  Intervention:   Drug: 3-dayIVM 200 mcg/kg/day/14-day 75mgASA/day + standard of care (intervention 1)
  Sponsors:   Makerere University;   Ministry of Health, Uganda;   Mbarara University of Science and Technology;   Joint Clinical Research Center
  Not yet recruiting

• The Safety and Efficacy of FB2001 in Healthy Subjects and Patients With COVID-19 Infection - Condition:   Covid19
  Interventions:   Drug: FB2001;   Drug: FB2001 Placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Not yet recruiting

• COVID-19 Antithrombotic Rivaroxaban Evaluation - Condition:   COVID-19
  Intervention:   Drug: Rivaroxaban 10 mg
  Sponsors:   Hospital Alemão Oswaldo Cruz;   Bayer;   Hospital Israelita Albert Einstein;   Hospital do Coracao;   Hospital Sirio-Libanes;   Hospital Moinhos de Vento;   Brazilian Research In Intensive Care Network;   Brazilian Clinical Research Institute
  Recruiting

• A Safety and Efficacy Study of Human Monoclonal Antibodies, BRII-196 and BRII-198 for the Treatment of Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: BRII-196 and BRII-198;   Drug: Placebo
  Sponsor:   Brii Biosciences, Inc.
  Not yet recruiting

• Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection - Conditions:   Covid19;   SARS-CoV 2
  Intervention:   Other: Sampling by venipuncture
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Recruiting

• Effect of Prone Position onV/Q Matching in Non-intubated Patients With COVID-19 - Condition:   Covid19
  Intervention:   Other: prone position
  Sponsor:   Southeast University, China
  Not yet recruiting

• Protecting Native Families From COVID-19 - Condition:   COVID-19
  Interventions:   Behavioral: Motivational Interviewing;   Behavioral: COVID-19 Symptom Monitoring System;   Behavioral: Motivational Interviewing and COVID-19 Symptom Monitoring System;   Other: Supportive Services
  Sponsor:   Johns Hopkins Bloomberg School of Public Health
  Not yet recruiting

• Honey and Nigella Sativa in COVID-19 Prophylaxis - Condition:   Covid19
  Interventions:   Drug: Honey;   Drug: Nigella sativa seed;   Other: Placebo
  Sponsor:   Sohaib Ashraf
  Recruiting

• Oxidative Stress Parameters, Trace Element and Quality of Life in Women Before and After Covid-19 Vaccines - Condition:   Covid-19 Vaccine
  Intervention:   Biological: CoronoVac Vaccine
  Sponsors:   Izmir Bakircay University;   Cigli Regional Training Hospital;   Muğla Sıtkı Koçman University
  Not yet recruiting

• Safety and Efficacy of Thymic Peptides in the Treatment of Hospitalized COVID-19 Patients in Honduras - Condition:   COVID-19
  Intervention:   Biological: Thymic peptides
  Sponsors:   Universidad Católica de Honduras;   Pontificia Universidad Catolica de Chile
  Recruiting

• Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  Not yet recruiting

• Pulmonary Rehabilitation of Patients With a History of COVID-19 - Condition:   Covid19
  Intervention:   Procedure: Pulmonary rehabilitation
  Sponsor:   University of Rzeszow
  Enrolling by invitation

• Trial Efficacy of Saisei Pharma Dietary Supplements MAF Capsules, 148 mg and M Capsules, 148 mg in Hospitalized COVID-19 Patients - Condition:   Covid19
  Interventions:   Dietary Supplement: MAF capsules 148 mg;   Dietary Supplement: M capsules 148 mg;   Other: Standard of care
  Sponsor:   Saisei Pharma
  Active, not recruiting

• Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Intervention:   Drug: Tofacitinib
  Sponsor:   I.M. Sechenov First Moscow State Medical University
  Completed

From PubMed

• A pilot double-blind safety and feasibility randomised controlled trial of high-dose intravenous zinc in hospitalised COVID-19 patients - CONCLUSION: Hospitalised COVID-19 patients demonstrated zinc deficiency. This can be corrected with HDIVZn. Such treatment appears safe, feasible and only associated with minimal peripheral infusion site irritation. This pilot study justifies further investigation of this treatment in COVID-19 patients. This article is protected by copyright. All rights reserved.

• Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response - The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A…

• Role of IL-6 inhibitor in treatment of COVID-19-related cytokine release syndrome - Cytokine release syndrome (CRS) may be the key factor in the pathology of severe coronavirus disease 2019 (COVID-19). As a major driver in triggering CRS in patients with COVID-19, interleukin-6 (IL-6) appears to be a promising target for therapeutics. The results of inhibiting both trans- and classical- signaling with marketed IL-6 inhibitors (tocilizumab, siltuximab and sarilumab) in severe COVID-19 patients are effective based on several small studies and case reports thus far. In this…

• The ORF8 Protein of SARS-CoV-2 Induced Endoplasmic Reticulum Stress and Mediated Immune Evasion by Antagonizing Production of Interferon Beta - The open reading frame 8 (orf8) is an accessory protein of SARS-CoV-2. It has 121 amino acids with two genotypes, orf8L and orf8S. In this study, we overexpressed the orf8L and orf8S of SARS-CoV-2 as well as the orf8b of SARS-CoV to investigate their roles in the regulation of endoplasmic reticulum (ER) stress and the inhibition of interferon beta (IFNß) production. We found that the two genotypes of SARS-CoV-2 orf8 are capable of inducing ER stress without significant difference by triggering…

• A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation - Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a…

• A comparative analysis of SARS-CoV-2 antivirals characterizes 3CL(pro) inhibitor PF-00835231 as a potential new treatment for COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CL^(pro) (M^(pro)). The drug candidate PF-00835231 is the active compound of the first anti-3CL^(pro) regimen…

• The Experience of Greece as a Model to Contain COVID-19 Infection Spread - The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) emerged in late 2019 and has caused a pandemic known as corona virus disease 2019 (COVID-19), responsible for the death of more than 2 million people worldwide. The outbreak of COVID-19 has posed an unprecedented threat on human lives and public safety. The aim of this review is to describe key aspects of the bio-pathology of the novel disease, and discuss aspects of its spread, as well as targeted protective strategies that can…

• Homozygosity for rs17775810 Minor Allele Associated With Reduced Mortality of COVID-19 in the UK Biobank Cohort - CONCLUSION: The rs17775810 analysis corroborates the favorable effect of fluvoxamine on COVID-19 survival.

• Comparative Genomics and Integrated Network Approach Unveiled Undirected Phylogeny Patterns, Co-mutational Hot Spots, Functional Cross Talk, and Regulatory Interactions in SARS-CoV-2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in 92 million cases in a span of 1 year. The study focuses on understanding population-specific variations attributing its high rate of infections in specific geographical regions particularly in the United States. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d, and e (subtypes e1 and e2). Clade d and subclade e2 were found…

• Dual Nature of Type I Interferons in SARS-CoV-2-Induced Inflammation - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ability of our cells to secrete type I interferons (IFN-Is) is essential for the control of virus replication and for effective antiviral immune responses; for this reason, viruses have evolved the means to antagonize IFN-I. Inhibition of IFN-I production is pronounced in SARS-CoV-2 infection, which can impair the adaptive immune response and exacerbate…

• Autophagosome maturation stymied by SARS-CoV-2 - Many pathogens are capable of disrupting autophagy within host cells. In this issue of Developmental Cell, Miao et al. discover that the SARS-CoV-2 protein ORF3a inhibits autophagosome-lysosome fusion by dysregulating the HOPS complex.

• Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors - The COVID-19 pandemic has clearly brought the healthcare systems world-wide to a breaking point along with devastating socioeconomic consequences. The SARS-CoV-2 virus which causes the disease uses RNA capping to evade the human immune system. Non-structural protein (nsp) 14 is one of the 16 nsps in SARS-CoV-2 and catalyzes the methylation of the viral RNA at N7-guanosine in the cap formation process. To discover small molecule inhibitors of nsp14 methyltransferase (MT) activity, we developed…

• Applying the CiPA Approach to Evaluate Cardiac Proarrhythmia Risk of some Antimalarials Used Off-label in the First Wave of COVID-19 - We applied a set of in silico and in vitro assays, compliant with the CiPA (Comprehensive In Vitro Proarrhythmia Assay) paradigm, to assess the risk of chloroquine or hydroxychloroquine-mediated QT prolongation and Torsades de Pointes (TdP), alone and combined with erythromycin and azithromycin, drugs repurposed during the first wave of COVID-19. Each drug or drug combination was tested in patch clamp assays on 7 cardiac ion channels, in in silico models of human ventricular electrophysiology…

• Tetracycline as an inhibitor to the SARS-CoV-2 - The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an extant threat against public health on a global scale. Cell infection begins when the spike protein of SARS-CoV-2 binds with the human cell receptor, angiotensin-converting enzyme 2 (ACE2). Here, we address the role of tetracycline as an inhibitor for the receptor-binding domain (RBD) of the spike protein. Targeted molecular investigation show that tetracycline binds more favorably to the RBD (-9.40 kcal/mol)…

• Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients - Hospitalized COVID-19 patients often present with a large spectrum of clinical symptoms. There is a critical need to better understand the immune responses to SARS-CoV-2 that lead to either resolution or exacerbation of the clinical disease. Here, we examine longitudinal plasma samples from hospitalized COVID-19 patients with differential clinical outcome. We perform immune-repertoire analysis including cytokine, hACE2-receptor inhibition, neutralization titers, antibody epitope repertoire,…

From Patent Search

• SARS-COV-2 BINDING PROTEINS - - link

• Compositions and methods for detecting SARS-CoV-2 spike protein - - link

• 稳定的冠状病毒重组蛋白二聚体及其表达载体 - 本发明公开了稳定的冠状病毒重组蛋白二聚体及其表达载体，冠状病毒重组蛋白，由冠状病毒S蛋白S‑RBD、冠状病毒N蛋白的CTD区N‑CTD和将二者偶联的连接子构成。本发明一些实例的冠状病毒重组蛋白，可以形成并维持稳定的二聚体结构，避免单体S‑RBD降解，有利于提高冠状病毒重组蛋白的免疫原性，有望用于制备检测试剂原料、疫苗、抗体、预防或治疗性药物。本发明一些实例的冠状病毒重组蛋白二聚体，具有很好的免疫原性。在疫苗开发领域具有广阔的应用前景。本发明一些实例的表达载体，易于表达冠状病毒重组蛋白二聚体且表达量高。 - link

• SELF-CLEANING AND GERM-KILLING REVOLVING PUBLIC TOILET FOR COVID 19 - - link

• Deep Learning Based System for the Detection of COVID-19 Infections - - link

• 新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒 - 本发明提供一种新冠病毒疫苗表达抗原蛋白的电化学发光免疫检测试剂盒，所述试剂盒至少包含：包被有链霉亲和素的孔板、生物素标记的抗新冠棘突蛋白抗体1、SULFO标记的抗新冠棘突蛋白抗体2、洗涤液、读数液、新冠病毒S蛋白标准品和新冠病毒RBD蛋白标准品。本发明以生物素标记的抗新冠棘突蛋白的抗体1与链霉亲和素板进行连接作为固定相，以新冠S蛋白、RBD蛋白作为参照品，可被SULFO标记的抗体2识别，从而检测新冠抗原的表达情况。该试剂盒能准确灵敏地定量检测不同基质中的新冠S蛋白、RBD蛋白，样品的前处理过程简单，耗时少，可同时检测大量样品。本发明对于大批量样品的新冠病毒疫苗表达抗原的检测具有重要意义。 - link

• 陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层 - 本发明是关于一种陶瓷复合涂料、杀毒陶瓷复合涂料及其制备方法和涂层。该涂料包括30_{99.9%无机树脂、0.1}70%氮化硅、0_{10%功能助剂、0}18%无机颜料和0_{2%其他功能助剂；无机树脂由有机烷氧基硅烷、有机溶剂和硅溶胶混合、反应，抽醇，添加去离子水获得；有机烷氧基硅烷、有机溶剂和硅溶胶的质量比为1}1.6：0.5~0.8：1。所要解决的技术问题是如何制备一种贮存稳定性好、可常温固化且膜层的物理化学性能优异的涂料；该涂料VOC含量低，具有良好的安全生产性，且涂料成膜过程中的VOC排放很低，利于环保；该膜层的硬度高、柔韧性好，不易开裂，且可以接触性杀灭病毒和细菌；该涂料既可常温固化，也可加热固化，无需现场两个剂型调配，施工方便，成本节约，从而更加适于实用。 - link

• SARS-CoV-2 antibodies - - link

• 利用BLI技术检测新型冠状病毒中和性抗体的方法 - 本发明提供一种利用BLI技术检测新型冠状病毒中和性抗体的方法，先将同一浓度的人ACE2蛋白捕获到生物传感器表面上，再将新型冠状病毒棘突蛋白RBD分别与不同浓度的待测中和性抗体预混，再将各混合液分别与捕获到生物传感器表面上的人ACE2蛋白接触，根据基于BLI技术的分子互作仪器检测到的干涉光谱的相对位移强度变化计算抑制率，绘制抑制曲线，计算IC50。本发明操作简单，快速高效，检测全过程无需包被和反复加样、洗板，15min内即可得到实验结果。检测反应在黑色孔板中进行，可实现大批量样品的新冠中和抗体的检测，与传统定性检测不同，通过计算IC50值，可以快速比较不同新冠中和性抗体的抑制能力。 - link

• SARS-CoV-2 antibodies - - link