Covid-19 Sentry

Contents

• From Preprints
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From Preprints

• Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death -
  Most Covid-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was Covid-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothel, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced Covid-19 ARDS.
  🖺 Full Text HTML: Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death
• The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study -
  The N501Y mutation in Covid-19 arise many question but a small amount of data are currently available. An urgent understanding of N501Y mechanism of action at molecular level is highly required. Here, we present the preliminary results of our Free energy perturbation (FEP) and Molecular dynamics (MD) calculations for the interaction of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody, STE90-C11, derived from COVID-19 patients. The results shown that the S1 RBD-ACE2 interaction was increased whereas those with the STE90-C11 antibody significantly decreased (over about 160 times). This may explain the observed in UK more spread of the virus but also emerge an important question about the possible human immune response and already available vaccines. Indeed, the latter may still act well but our data indicate some possible reduction of their effect. Further studies of N501Y mutation are need.
  🖺 Full Text HTML: The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
• Genomic diversity of SARS-CoV-2 can be accelerated by a mutation in the nsp14 gene -
  Nucleotide substitution rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is relatively low compared to the other RNA viruses because coronaviruses including SARS-CoV-2 encode non-structural protein 14 (nsp14) that is an error-correcting exonuclease protein. In this study, to understand genome evolution of SARS-CoV-2 in the current pandemic, we examined mutations of SARS-CoV-2 nsp14 which could inhibit its error-correcting function. First, to obtain functionally important sites of nsp14, we examined 62 representative coronaviruses belonging to alpha, beta, gamma, delta, and unclassified coronaviruses. As a result, 99 out of 527 amino acid sites of nsp14 were evolutionarily conserved. We then examined nsp14 sequences obtained from 28,082 SARS-CoV-2 genomes and identified 6 amino acid changes in nsp14 mutants that were not detected in the 62 representative coronaviruses. We examined genome substitution rates of these mutants and found that an nsp14 mutant with a proline to leucine change at position 203 (P203L) showed a higher substitution rate (35.9 substitutions/year) than SARS-CoV-2 possessing wild-type nsp14 (19.8 substitutions/year). We confirmed that the substitution rate of the P203L is significantly higher than those of other variants containing mutations in structural proteins. Although the number of SARS-CoV-2 variants containing P203L mutation of nsp14 is limited (26), these mutants appeared at least 10 times independently in the current pandemic. These results indicated that the molecular function of nsp14 is important for survival of various coronaviruses including SARS-CoV-2 and that some mutations such as P203L of nsp14 inhibiting its error-correcting function are removed rapidly due to their deleterious effects.
  🖺 Full Text HTML: Genomic diversity of SARS-CoV-2 can be accelerated by a mutation in the nsp14 gene
• TCR meta-clonotypes for biomarker discovery with tcrdist3: quantification of public, HLA-restricted TCR biomarkers of SARS-CoV-2 infection -
  As the mechanistic basis of adaptive cellular antigen recognition, T cell receptors (TCRs) encode clinically valuable information that reflects prior antigen exposure and potential future response. However, despite advances in deep repertoire sequencing, enormous TCR diversity complicates the use of TCR clonotypes as clinical biomarkers. We propose a new framework that leverages antigen-enriched repertoires to form meta-clonotypes -- groups of biochemically similar TCRs -- that can be used to robustly quantify functionally similar TCRs in bulk repertoires. We apply the framework to TCR data from COVID-19 patients, generating 1,915 public TCR meta-clonotypes from the 18 SARS-CoV-2 antigen-enriched repertoires with the strongest evidence of HLA-restriction. Applied to independent cohorts, meta-clonotypes targeting these specific epitopes were more frequently detected in bulk repertoires compared to exact amino acid matches, and 44% (845/1915) were significantly enriched among COVID-19 patients that expressed the putative restricting HLA allele, demonstrating the potential utility of meta-clonotypes as antigen-specific features for biomarker development. To enable further applications, we developed an open-source software package, tcrdist3, that implements this framework and facilitates workflows for distance-based TCR repertoire analysis.
  🖺 Full Text HTML: TCR meta-clonotypes for biomarker discovery with tcrdist3: quantification of public, HLA-restricted TCR biomarkers of SARS-CoV-2 infection
• Influence of HLA class II polymorphism on predicted cellular immunity against SARS-CoV-2 at the population and individual level -
  Development of effective adaptive immune responses after coronavirus disease 2019 (COVID-19) and after vaccination against SARS-CoV-2 is predicated on recognition of viral peptides, presented in the context of HLA class II molecules, by CD4+ T-cells. We capitalised on extensive high resolution HLA data deposited in the National Marrow Donor Program registry to obtain detailed information on human HLA haplotype frequencies of twenty five human populations and used a bioinformatics approach to investigate the role of HLA polymorphism on SARS-CoV-2 immunogenicity at the population and at the individual level. Within populations, we identify wide inter-individual variability in predicted CD4+ T-cell reactivity against structural, non-structural and accessory SARS-CoV-2 proteins, according to expressed HLA genotype. However, we find similar potential for anti-SARS-CoV-2 cellular immunity at the population level, across all ethnic groups examined, suggesting that HLA polymorphism is unlikely to account for observed disparities in clinical outcomes after COVID-19 among different race and ethnic groups. We predict robust immune reactivity against SARS-CoV-2 Spike protein, the basis for the majority of current vaccination efforts, both at the population and individual level, despite significant variation in Spike-derived peptide presentation by individual HLA genotypes. Finally, we provide comprehensive maps of SARS-CoV-2 proteome immunogenicity accounting for population coverage in major ethnic groups. Our findings provide important insight on the potential role of HLA polymorphism on development of protective immunity after SARS-CoV-2 infection and after vaccination and a firm basis for further experimental studies in this field.
  🖺 Full Text HTML: Influence of HLA class II polymorphism on predicted cellular immunity against SARS-CoV-2 at the population and individual level
• Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2 -
  Within the last two decades, severe acute respiratory syndrome (SARS) coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks. For reasons yet to be fully understood the COVID-19 outbreak caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1, despite striking similarities between the two viruses. One of the most variable genes differentiating SARS-CoV-1 and SARS-CoV-2 is the S gene that encodes the spike glycoprotein. This protein mediates a crucial step in the infection, i.e., host cell recognition and viral entry, which starts with binding to the host cell angiotensin converting enzyme 2 (ACE2) protein for both viruses. Recent structural and functional studies have shed light on the differential binding behavior of the SARS-CoV-1 and SARS-CoV-2 spike proteins. In particular, cryogenic electron microscopy (cryo-EM) studies show that ACE2 binding is preceded by a large-scale conformational change in the spike protein to expose the receptor binding domain (RBD) to its binding partner. Unfortunately, these studies do not provide detailed information on the dynamics of this activation process. Here, we have used an extensive set of unbiased and biased microsecond-timescale all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and SARS-CoV-2 spike protein ectodomains in explicit solvent to determine the differential behavior of spike protein activation in the two viruses. Our results based on nearly 50 microseconds of equilibrium and nonequilibrium MD simulations indicate that the active form of the SARS-CoV-2 spike protein is considerably more stable than the active SARS-CoV-1 spike protein. Unlike the active SARS-CoV-2 spike, the active SARS-CoV-1 spike spontaneously undergoes a large-scale conformational transition to a pseudo-inactive state, which occurs in part due to interactions between the N-terminal domain (NTD) and RBD that are absent in the SARS-CoV-2 spike protein. Steered MD (SMD) simulations indicate that the energy barriers between active and inactive states are comparatively lower for the SARS-CoV-1 spike protein. Based on these results, we hypothesize that the greater propensity of the SARS-CoV-2 spike protein to remain in the active conformation contributes to the higher transmissibility of SARS-CoV-2 in comparison to SARS-CoV-1. These results strongly suggest that the differential binding behavior of the active SARS-CoV-1 and 2 spike proteins is not merely due to differences in their RBDs as other domains of the spike protein such as the NTD could play a crucial role in the effective binding process, which involves the pre-binding activation. Therefore, our hypothesis predicts that mutations in regions such as the NTD, which is not directly involved in binding, may lead to a change in the effective binding behavior of the coronavirus.
  🖺 Full Text HTML: Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2
• Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes -
  Many antibody and immune escape variants in SARS-CoV-2 are now documented in literature. The availability of SARS-CoV-2 genome sequences enabled us to investigate the occurrence and genetic epidemiology of the variants globally. Our analysis suggests that a number of genetic variants associated with immune escape have emerged in global populations.
  🖺 Full Text HTML: Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes
• Support and follow-up needs of patients discharged from Intensive Care after severe COVID-19: a mixed-methods study of the views of UK general practitioners and intensive care staff during the pandemic's first wave -

  Background: After discharge from an intensive care unit(ICU), over 50% of patients face significant physical, mental and cognitive problems. The COVID-19 pandemic has resulted in a large cohort of these patients who will need follow-up services that can address their support needs. Objectives: To identify follow-up services planned for COVID-19 patients discharged from ICU, and to explore the views of ICU staff and General Practitioners(GPs) regarding these patients9 future needs and care coordination. Design: Sequential mixed-methods UK study. We explored usual follow-up practice after ICU discharge and changes in follow-up during the pandemic through a survey of ICU staff, and GP awareness of follow-up and support needs of patients discharged from ICU through a survey of GPs. Through these surveys, we identified participants for semi-structured interviews with both groups. Results: We obtained 170 survey responses and conducted 23 interviews. Over 60% of GPs were unaware of the follow-up services generally provided by their local hospitals, and whether or not these were functioning during the pandemic. Eighty percent of ICUs reported some form of follow-up services, with 25% of these suspending provision during the peak of the pandemic, and over half modifying their provision (usually to provide the service remotely). Complex funding streams, poor communication between primary and secondary care, and lack of clarity about who was responsible for referrals and follow-up were the most common problems identified. Discharge documentation was described as poor and lacking key information. Both groups mentioned difficulties accessing services in the community. Conclusions: The pandemic has highlighted long-standing issues of continuity of care and complex funding streams for post-ICU follow-up care. The large cohort of ICU patients admitted due to COVID-19 highlights the need for improved follow-up services and communication between specialists and GPs, not only for COVID-19 patients, but for all those discharged from ICU.

  🖺 Full Text HTML: Support and follow-up needs of patients discharged from Intensive Care after severe COVID-19: a mixed-methods study of the views of UK general practitioners and intensive care staff during the pandemic's first wave
• Oral clarithromycin in COVID-19 of moderate severity: the ACHIEVE open-label trial using concurrent matched comparators -

  Background: Clarithromycin clinical efficacy has not been described in COVID-19. Research question: Is oral clarithromycin beneficial for treating patients diagnosed with COVID-19? Study and methods: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted at four study sites in Greece between May and October 2020. Ninety participants with respiratory tract infections received clarithromycin 500 mg every 12 hours for 7 days; another 90 standard-of-care (SOC) propensity score-matched concurrent controls received azithromycin plus hydroxychloroquine. The composite primary endpoint was defined for patients with upper respiratory tract infection as: (a) no need for hospital re-admission or (b) lack of progression into lower respiratory tract infection and, for patients with lower respiratory tract infection, as at least 50% decrease of the score of respiratory symptoms at the end-of-treatment (EOT) without progression into severe respiratory failure (SRF). The incidence SRF at the test-of-cure (TOC) on day 14 was a secondary endpoint. For clarithromycin-treated patients, viral load of SARS-CoV-2, biomarkers, the function of mononuclear cells, and safety were assessed; biomarkers were also measured in SOC comparators. Results: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%) and 73.3% of concurrent SOC comparators (95%CIs; 63.4-81.4%). The odds ratio for the primary endpoint with clarithromycin treatment in univariate analysis was 2.36 (95%CIs 1.09-5.08; P: 0.039). Results were confirmed after multivariate stepwise logistic regression analysis (odds ratio 3.30; 95% CI 1.10-9.87; P: 0.033). At the TOC visit, the incidence of SRF was 12.2% (n = 11 ; 95%CIs 6.9-20.6%) among patients treated with clarithromycin (odds ratio for SRF 0.38; 95%CIs 0.17-0.84) versus 26.7% (n= 24; 95%CIs 18.6-36.6%) among concurrent SOC comparators (P: 0.023). Clarithromycin use was associated with decreases in circulating levels of C-reactive protein, of tumour necrosis factor-alpha and of interleukin (IL)-6; by an increase of the ratio of Th1 to Τh2 mononuclear responses; and by suppression of SARS-CoV-2 relative viral load. No safety concerns were reported. Patients starting clarithromycin with the first five days from symptoms onset achieved better responses. Interpretation: Clarithromycin treatment is associated with early clinical improvement in patients with moderate COVID-19. Modulation of the Th1/Th2 responses is proposed as the mechanism of action.

  🖺 Full Text HTML: Oral clarithromycin in COVID-19 of moderate severity: the ACHIEVE open-label trial using concurrent matched comparators
• MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19 in the Israeli population -

  HLA haplotypes were found to be associated with increased risk for viral infections or disease severity in various diseases, including SARS. Several genetic variants are associated with Covid-19 severity. However, no clear association between HLA and Covid-19 incidence or severity has been reported. We conducted a large scale HLA analysis of Israeli individuals who tested positive for SARS-CoV-2 infection by PCR. Overall, 72,912 individuals with known HLA haplotypes were included in the study, of whom 6,413 (8.8%) were found to have SARS-CoV-2 by PCR. a Total of 20,937 subjects were of Ashkenazi origin (at least 2/4 grandparents). One hundred eighty-one patients (2.8% of the infected) were hospitalized due to the disease. None of the 66 most common HLA loci (within the five HLA subgroups; A, B, C, DQB1, DRB1) was found to be associated with SARS-CoV-2 infection or hospitalization. Similarly, no association was detected in the Ashkenazi Jewish subset. Moreover, no association was found between heterozygosity in any of the HLA loci and either infection or hospitalization. We conclude that HLA haplotypes are not a major risk/protecting factor among the Israeli population for SARS-CoV-2 infection or severity.

  🖺 Full Text HTML: MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19 in the Israeli population
• Does COVID-19 Testing Create More Cases? An Empirical Evidence on the Importance of Mass Testing During a Pandemic -

  The importance of testing and surveillance of an infectious disease cannot be underestimated. The testing is the first step to detect an infectious disease, and mass testing can slow or mitigate the spread of an infectious disease. Despite overwhelming evidence and the importance of testing discussed in the literature, there have been claims that "more COVID-19 testing creates more cases". Therefore, there is a need to study whether massive testing is the reason for detecting more positive COVID-19 cases. In this research, we used a dataset from the U.S. Department of Health & Human Services and empirically showed that by increasing the COVID-19 testing in the U.S., the spread of the COVID-19 decreased significantly. Our results indicate a negative relationship between the number of positive cases and the number of tests performed in the past months. The large-scale testing may have helped identify positive and asymptomatic cases early in the course of illness, which enabled individuals to isolate themselves, thus reducing the chances of spreading the diseases and slowing the spread of the pandemic.

  🖺 Full Text HTML: Does COVID-19 Testing Create More Cases? An Empirical Evidence on the Importance of Mass Testing During a Pandemic
• Seropositivity in blood donors and pregnant women during 9-months of SARS-CoV-2 transmission in Stockholm, Sweden -

  Public health strategies to contain the pandemic continue to vary markedly across the world. In Sweden, compared to most advanced economies, social restrictions have primarily relied upon voluntary adherence to a set of recommendations and strict lockdowns have not been enforced. To better understand the development of humoral immunity to SARS-CoV-2 in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n=4,100) were sampled at random between 14th March-11th December 2020. All individuals (n=200/sampling week) were screened for anti-SARS-CoV-2 spike (S) trimer- and RBD-specific IgG responses with highly sensitive and specific ELISA assays, and the results were compared with those from historical controls (n=595). Data were modelled using a probabilistic Bayesian framework that considered individual responses to both antigens. We found that after a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second-wave of infections, approaching 15% of all individuals surveyed by 11th December. In agreement with the high transmission rate observed in the Stockholm area, seroprevalence in this cohort of active adults increased during the 9 months from the start of the outbreak, but was far from that required for herd immunity at the end of 2020.

  🖺 Full Text HTML: Seropositivity in blood donors and pregnant women during 9-months of SARS-CoV-2 transmission in Stockholm, Sweden
• Prognostic and predictive biomarkers in patients with COVID-19 treated with tocilizumab in a randomised controlled trial -

  Background Retrospective observational studies suggest that interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, lymphocytes, monocytes, neutrophils, D-dimer, and platelets are associated with disease progression, treatment outcomes, or both, in patients with COVID-19 pneumonia. We explored these candidate prognostic and predictive biomarkers with efficacy outcomes after treatment with tocilizumab, an anti-IL-6 receptor antibody using data from the COVACTA trial for patients hospitalised with severe COVID-19 pneumonia. Methods Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomisation) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Findings Modelling in the placebo arm showed all candidate biomarkers except LDH and D-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modelling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction p=0.03), mechanical ventilation (predictive interaction p=0.01), and clinical status (predictive interaction p=0.02) compared with placebo. Interpretation Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.

  🖺 Full Text HTML: Prognostic and predictive biomarkers in patients with COVID-19 treated with tocilizumab in a randomised controlled trial
• Characteristics of SARS-CoV-2 Testing for Rapid Diagnosis of COVID-19 during the Initial Stages of a Global Pandemic -

  Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. From January 11 - April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE=0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE=0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.

  🖺 Full Text HTML: Characteristics of SARS-CoV-2 Testing for Rapid Diagnosis of COVID-19 during the Initial Stages of a Global Pandemic
• Assessment of COVID-19 Pandemic in Nepal: A Lockdown Scenario Analysis -

  The Government of Nepal issued a nationwide lockdown from 24 March to 21 July 2020. Here we present the overall scenario of COVID-19, government efforts, impact on socio-economic, education, and health care, and prevailing challenges when the lockdown was lifted. We collated and analysed data provided by the Nepalese Ministry of Health and Population. There were only two confirmed cases from 610 Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests and no fatalities when the government introduced nationwide lockdown. Nepal had performed 7791 RT-PCR tests for COVID-19, the highest number of tests during the lockdown. It has recorded its highest daily rise in coronavirus infections with a total of 740 new cases from the total of 4483 RT-PCR tests performed on a single day. Nepal had reported a total of 17994 positive cases and 40 deaths at the end of lockdown. The spatial distribution clearly shows that the cases were rapidly spreading from the southern part of the country where most points of entry and exit from India are located. The government needs to allocate more resources, increase its capacity to test and trace, establish dedicated isolation and quarantine facilities, and impose local restrictions to manage potential COVID-19 outbreaks after easing lockdown.

  🖺 Full Text HTML: Assessment of COVID-19 Pandemic in Nepal: A Lockdown Scenario Analysis

From Clinical Trials

• Evaluation of the Efficacy of High Doses of Methylprednisolone in SARS-CoV2 ( COVID-19) Pneumonia Patients - Condition:   Covid19
  Intervention:   Drug: Methylprednisolone, Placebo
  Sponsor:   Azienda Unità Sanitaria Locale Reggio Emilia
  Not yet recruiting

• Changes in Viral Load in COVID-19 After Probiotics - Condition:   COVID-19
  Intervention:   Dietary Supplement: Dietary supplementation in patients with covid disease admitted to hospital
  Sponsors:   Hospital de Sagunto;   Biopolis S.L.;   Laboratorios Heel España
  Recruiting

• Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Hydroxychloroquine;   Behavioral: personal protective Measures
  Sponsor:   Benha University
  Completed

• Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19 - Condition:   Covid19
  Interventions:   Drug: Dalcetrapib;   Other: Placebo
  Sponsors:   DalCor Pharmaceuticals;   The Montreal Health Innovations Coordinating Center (MHICC);   Covance
  Not yet recruiting

• Phase 3 Inhaled Novaferon Study in Hospitalized Patients With Moderate to Severe COVID-19 - Condition:   Covid19
  Interventions:   Biological: Novaferon;   Biological: Placebo
  Sponsor:   Genova Inc.
  Not yet recruiting

• suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19 - Condition:   Covid19
  Interventions:   Drug: Anakinra;   Drug: Placebo
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Not yet recruiting

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

• Evaluating the Impact of EnteraGam In People With COVID-19 - Condition:   Covid19
  Interventions:   Dietary Supplement: Bovine Plasma-Derived Immunoglobulin Concentrate;   Other: Standard of care
  Sponsors:   Entera Health, Inc;   Lemus Buhils, SL;   Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)
  Not yet recruiting

• Efficacy and Safety of Remdesivir and Tociluzumab for the Management of Severe COVID-19: A Randomized Controlled Trial - Conditions:   Covid19;   Covid-19 ARDS
  Interventions:   Drug: Remdesivir;   Drug: Tocilizumab
  Sponsors:   M Abdur Rahim Medical College and Hospital;   First affiliated Hospital of Xi'an Jiaoting University
  Recruiting

• Inhaled Ivermectin and COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Ivermectin Powder
  Sponsor:   Mansoura University
  Not yet recruiting

• AZD1222 Vaccine in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   AstraZeneca;   R-Pharm
  Not yet recruiting

• Anti-COVID19 AKS-452 - ACT Study - Condition:   Covid19
  Intervention:   Biological: AKS-452
  Sponsors:   University Medical Center Groningen;   Akston Biosciences Corporation
  Not yet recruiting

• Mushroom-based Product for COVID-19 - Condition:   COVID-19
  Intervention:   Drug: FoTv
  Sponsors:   Gordon Saxe;   University of California, Los Angeles;   University of California, Irvine
  Recruiting

• Study to Investigate the Treatment Effect of Colchicine in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Colchicine;   Drug: Standard COVID-19 care
  Sponsors:   Ayub Teaching Hospital;   Universidad de Murcia
  Recruiting

• Evaluation of Prognostic Modification in COVID-19 Patients in Early Intervention Treatment - Condition:   Covid19
  Interventions:   Drug: Azithromycin / Ivermectin / Ribaroxaban / Paracetamol;   Drug: Azithromycin / Ribaroxaban / Paracetamol
  Sponsors:   Gilberto Cruz Arteaga;   Coordinación de Investigación en Salud, Mexico
  Recruiting

From PubMed

• Effects of Tocilizumab in COVID-19 patients: a cohort study - CONCLUSIONS: Majority of patients demonstrated clinical improvement and were successfully discharged alive from the hospital after receiving tocilizumab. We observed a rebound effect with CRP, which may suggest the need for higher or subsequent doses to adequately manage cytokine storm. Based on our findings, we believe that tocilizumab may have a role in the early treatment of COVID-19, however larger randomized controlled studies are needed to confirm this.

• Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19 - CONCLUSION: The in vitro activity of GaM against SARS-CoV-2, together with GaM's known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.

• Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform - BACKGROUND: Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.

• Identification of FDA approved drugs and nucleoside analogues as potential SARS-CoV-2 A1pp domain inhibitor: An in silico study - Coronaviruses are known to infect respiratory tract and intestine. These viruses possess highly conserved viral macro domain A1pp having adenosine diphosphate (ADP)-ribose binding and phosphatase activity sites. A1pp inhibits adenosine diphosphate (ADP)-ribosylation in the host and promotes viral infection and pathogenesis. We performed in silico screening of FDA approved drugs and nucleoside analogue library against the recently reported crystal structure of SARS-CoV-2 A1pp domain. Docking...

• Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA - Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East...

• Structure-Based Screening to Discover New Inhibitors for Papain-like Proteinase of SARS-CoV-2: An In Silico Study - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses a multifunctional papain-like proteinase (PLpro), which mediates the processing of the viral replicase polyprotein. Inhibition of PLpro has been shown to suppress the viral replication. This study aimed to explore new anti-PLpro candidates by applying virtual screening based on GRL0617, a known PLpro inhibitor of SARS coronavirus (SARS-CoV). The three-dimensional (3D) structure of SARS-CoV-2 PLpro was built by homology...

• A ligand selection strategy identifies chemical probes targeting the proteases of SARS-CoV-2 - Activity-based probes are valuable tools for chemical biology. However, finding probes that specifically target the active site of an enzyme remains a challenging task. Here we present a ligand selection strategy that allows to rapidly tailor electrophilic probes to a target of choice and showcase its application for the two cysteine proteases of SARS-CoV-2 as proof of concept. The resulting probes were specific for the active site labelling of 3CL pro and PL pro with sufficient selectivity in a...

• Spiky nanostructures for virus inhibition and infection prevention - The outbreak of a novel highly infectious virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has aroused people's concern about public health. The lack of ready-to-use vaccines and therapeutics makes the fight with these pathogens extremely difficult. To this point, rationally designed virus entry inhibitors that block the viral interaction with its receptor can be novel strategies to prevent virus infection. For ideal inhibition of the virus, the virus-inhibitor interaction...

• The SARS-CoV-2 RNA-protein interactome in infected human cells - Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome...

• Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension - The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics,...

• Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus - CONCLUSION: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.

• Action of dipeptidyl peptidase-4 inhibitors on SARS-CoV-2 main protease - In a recent publication in this journal Eleftheriou et al. proposed inhibitors of dipeptidyl peptidase-4 (DPP-4) to be functional inhibitors of the main protease (M pro ) of SARS-CoV-2. Their predictions prompted the authors to suggest linagliptin, a DPP-4 inhibitor and approved anti-diabetes drug, as a repurposed drug candidate against the ongoing COVID-19 pandemic. We used an enzymatic assay measuring inhibition of M pro catalytic activity in the presence of four different commercially...

• "Silent hypoxaemia in COVID-19 patients" - The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labeled with 'happy hypoxia,' in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key...

• Recognition of Plausible Therapeutic Agents to Combat COVID-19: An Omics Data Based Combined Approach - Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, more than 67,000 reference sequences including a complete genome sequence of SARS-CoV-2 isolate performed by us and several in silico techniques were merged to propose prospective therapeutics. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA...

• Understanding the immunopathogenesis of COVID-19: Its implication for therapeutic strategy - Although 80% of individuals infected with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) recover without antiviral treatments, the other 20% progress to severe forms of pulmonary disease, suggesting that the host's immune response to the virus could influence the outcome of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects alveolar epithelial type 2 cells expressing angiotensin-converting enzyme 2, and these infected epithelial cells recruit dendritic cells, neutrophils...

From Patent Search

• Covid 19 - Chewing Gum - - link

• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• The use of human serum albumin (HSA) and Cannabigerol (CBG) as active ingredients in a composition for use in the treatment of Coronavirus (Covid-19) and its symptoms - - link

• "AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2." - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex. - link

• 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염; 및 글루카곤 수용체 작용제(glucagon receptor agonist), 위 억제 펩타이드(gastric inhibitory peptide, GIP), 글루카곤-유사 펩타이드 1(glucagon-like peptide 1, GLP-1) 및 글루카곤 수용체/위 억제 펩타이드/글루카곤-유사 펩타이드 1(Glucagon/GIP/GLP-1) 삼중 완전 작용제(glucagon receptors, gastric inhibitory peptide and glucagon-like peptide 1 (Glucagon/GIP/GLP-1) triple full agonist)로 이루어진 군으로부터 선택된 1종 이상;을 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. - link

• Haptens, hapten conjugates, compositions thereof and method for their preparation and use - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels. - link

• SARS-CoV-2 RBD共轭纳米颗粒疫苗 - 本发明涉及免疫医学领域，具体而言，涉及一种SARS‑CoV‑2 RBD共轭纳米颗粒疫苗。该疫苗包含免疫原性复合物，所述免疫原性复合物包含：a）与SpyCatcher融合表达的载体蛋白自组装得到的纳米颗粒载体；b）与SpyTag融合表达的SARS‑CoV‑2病毒的RBD抗原；所述载体蛋白选自Ferritin、mi3和I53‑50；所述载体蛋白与所述抗原之间通过SpyCatcher‑SpyTag共价连接。 - link

• Устройство электронного контроля и дистанционного управления аппарата искусственной вентиляции легких - Полезная модель относится к медицинской технике, а именно к устройствам для воздействия на дыхательную систему пациента смесью различных газов, в частности, к устройствам для проведения искусственной вентиляции легких (ИВЛ). Технический результат предлагаемой полезной модели заключается в решении технической проблемы, состоящей в необходимости расширения арсенала технических средств, предназначенных для электронного контроля и управления ИВЛ, путем реализации возможности дистанционного управления аппаратами ИВЛ в медицинских учреждениях, не оборудованных кабельными вычислительными сетями. Указанный технический результат достигается благодаря тому, что в известное устройство электронного контроля и дистанционного управления аппарата ИВЛ, содержащее центральный микроконтроллер, а также программно-аппаратные средства управления функциями доставки воздушной смеси пациенту и многоуровневой тревожной сигнализации об отклонениях от нормативных условий и технических неполадках в аппарате ИВЛ, введены связанные друг с другом микроконтроллер связи и дистанционного управления и радиомодем, выполненный с возможностью связи с точками доступа радиканальной сети, при этом центральный микроконтроллер устройства выполнен с дополнительными входом/выходом, которые связаны с управляющими выходом/входом микроконтроллера связи и дистанционного управления, а, в зависимости от типа применяемой в медицинском учреждении радиоканальной сети связи и передачи данных, радиомодем может быть выполнен в виде интерфейсного аудиомодуля Bluetooth 4.0 BLE, приемопередающего модуля Wi-Fi либо устройства "малого радиуса действия", работающего по технологии LoRa на нелицензируемых частотах мегагерцового диапазона, например, в диапазоне 868 МГц. 3 з.п. ф-лы, 1 ил. - link