Covid-19 Sentry

Contents

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

From Preprints

• S-variant SARS-CoV-2 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-PCR -

  Birmingham University Turnkey laboratory is part of the Lighthouse network responsible for testing clinical samples under the UK government Test & Trace scheme. Samples are analysed for the presence of SARS-CoV-2 in respiratory samples using the Thermofisher TaqPath RT-PCR test, which is designed to co-amplify sections of three SARS-CoV-2 viral genes. Since more recent information became available regarding the presence of SARS-CoV-2 variants of concern (S-VoC), which can show a suboptimal profile in RT-PCR tests such as the ThermoFisher TaqPath used at the majority of Lighthouse laboratories, we analysed recently published data for trends and significance of the S-gene dropout variant. Results showed that: (i) the population of S-gene dropout samples had significantly lower median Ct values of ORF and N-gene targets compared to samples where S-gene was detected (ii) on a population basis, S-gene dropout samples clustered around very low Ct values for ORF and N targets (iii) linked Ct values for individual samples showed that a low Ct for ORF and N were clearly associated with an S-dropout characteristic (iv) when conservatively inferring relative viral load from Ct values, approximately 35% of S-dropout samples had high viral loads between 10 and 10,000-fold greater than 1 x 106, compared to 10% of S-positive samples. This analysis suggests that patients whose samples exhibit the S-dropout profile in the TaqPath test are more likely to have high viral loads at the time of sampling. The relevance of this to epidemiological reports of fast spread of the SARS-CoV-2 in regions of the UK is discussed.

  🖺 Full Text HTML: S-variant SARS-CoV-2 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-PCR
• Quantifying the online news media coverage of the COVID-19 pandemic. -

  Background. Non-pharmaceutical interventions such as lockdowns, mask wearing and social distancing have been the primary measures to effectively combat the COVID-19 pandemic. Such measures are highly effective when there is strong population wide adherence which needs to be facilitated by information on the current risks posed by the pandemic alongside a clear exposition of the rules and guidelines in place. Here we address the issue of communication on the pandemic by offering data and analysis of online news media coverage of COVID-19. Methods. We collected 26 million news articles from the front pages of 172 major online news sources in 11 countries (available at http://sciride.org). Using topic detection we identified COVID-19-related content to quantify the proportion of total coverage pandemic received in 2020. Sentiment analysis tool Vader was employed to stratify the emotional polarity of COVID-19 reporting. Further topic detection and sentiment analysis was performed on COVID-19 articles to reveal the leading themes in pandemic reporting and their respective emotional polarizations. Findings. We find that COVID-19 coverage accounted for approximately 25% of all front-page online news articles between January and October 2020. Sentiment analysis of English-speaking sources reveals that the overall COVID-19 coverage cannot be simply classified as negative due to the disease subject matter, suggesting a wide heterogeneous reporting of the pandemic. Within this heterogenous coverage, 16% of COVID-19 news articles (or 4% of all English-speaking articles) can be classified as highly negatively polarized, citing issues such as death, fear or crisis. Interpretation. The goal of pandemic public health communication is to increase understanding of distancing rules and maximize the impact of any governmental policy. Our results suggest an information overload in COVID-19 reporting that could risk obscuring effective policy communication. We hope that our data and analysis will inform health communication strategy to minimize the risks of COVID-19 while vaccination regimes are being introduced.

  🖺 Full Text HTML: Quantifying the online news media coverage of the COVID-19 pandemic.
• Salivary SARS-CoV-2 antigen rapid detection: a prospective cohort study -

  Background: SARS-CoV-2 quick testing and reporting are now considered relevant for the containment of new pandemic waves. Antigen testing in self-collected saliva might be useful. We compared the diagnostic performance of salivary and naso-pharyngeal swab (NPS) SARS-CoV-2 antigen detection by a rapid chemiluminescent assay (CLEIA) and two different point-of-care (POC) immunochromatographic assays, with that of molecular testing. Methods. 234 patients were prospectively enrolled. Paired self-collected saliva (Salivette) and NPS were obtained to perform rRT-PCR, chemiluminescent (Lumipulse G) and POC (NPS: Fujirebio and Abbott; saliva: Fujirebio) for SARS-CoV-2 antigen detection. Results. The overall agreement between NPS and saliva rRT-PCR was 78.7%, reaching 91.7% at the first week from symptoms onset. SARS-CoV-2 CLEIA antigen was highly accurate in distinguishing between positive and negative NPS (ROC-AUC=0.939, 95%CI:0.903-0.977), with 81.6% sensitivity and 93.8% specificity. This assay on saliva had an overall good accuracy (ROC- AUC=0.805, 95%CI:0.740-0.870), reaching the optimal value within 7 days from symptom onset (Sensitivity: 72%; Specificity: 97%). POC antigen in saliva had a very limited sensitivity (13%), performing better in NPS (Sensitivity: 48% and 66%; Specificity: 100% and 99% for Espline and Abbott respectively), depending on viral loads. Conclusions: Self-collected saliva is a valid alternative to NPS for SARS-CoV-2 detection not only by molecular, but also by CLEIA antigen testing, for which the highest diagnostic accuracy was achieved in the first week from symptom onset. Saliva is not suitable for POC, although the accuracy of these tests appears satisfactory for NPS with high viral load.

  🖺 Full Text HTML: Salivary SARS-CoV-2 antigen rapid detection: a prospective cohort study
• Spatial Allocation of Scarce Vaccine and Antivirals for COVID-19 -

  Although the COVID-19 disease burden is heterogeneous across space, the U.S. National Academies of Sciences, Engineering, and Medicine recommends an equitable spatial allocation of pharmaceutical interventions based, for example, on population size, in the interest of speed and workability. Utilizing economic-epidemiological modeling, we benchmark the performance of ad hoc allocation rules of scarce vaccines and drugs by comparing them to the rules for a vaccine and for a drug treatment that minimize the economic damages and expenditures over time, including a penalty cost representing the social costs of deviating from an ad hoc allocation. Under different levels of vaccine and drug scarcity, we consider scenarios where length of immunity and compliance to travel restrictions vary, and consider the robustness of the rules when assumptions regarding these factors are incorrect. Because drugs and vaccines attack different points in the disease pathology, the benefits from deviating from the ad hoc rule differ. For drug treatment, optimal policies often allocate all available treatments to one jurisdiction for a period of time, while ad hoc rules act to spread out treatments across jurisdictions. For vaccines, the benefits from deviating are especially high when immunity is permanent, when there is compliance to travel restrictions, and when the supply of vaccine is low. Interestingly, a lack of compliance to travel restrictions pushes the optimal allocations of vaccine towards the ad hoc and improves the relative robustness of the ad hoc rules, as the mixing of the populations reduces the spatial heterogeneity in disease burden.

  🖺 Full Text HTML: Spatial Allocation of Scarce Vaccine and Antivirals for COVID-19
• Using Test Positivity and Reported Case Rates to Estimate State-Level COVID-19 Prevalence and Seroprevalence in the United States -

  Accurate estimates of infection prevalence and seroprevalence are essential for evaluating and informing public health responses needed to address the ongoing spread of COVID-19 in the United States. A data-driven Bayesian single parameter semi-empirical model was developed and used to evaluate state-level prevalence and seroprevalence of COVID-19 using daily reported cases and test positivity ratios. COVID-19 prevalence is well-approximated by the geometric mean of the positivity rate and the reported case rate. As of December 8, 2020, we estimate nation-wide a prevalence of 1.4% [Credible Interval (CrI): 0.8%-1.9%] and a seroprevalence of 11.1% [CrI: 10.1%-12.2%], with state-level prevalence ranging from 0.3% [CrI: 0.2%-0.4%] in Maine to 3.0% [CrI: 1.1%-5.7%] in Pennsylvania, and seroprevalence from 1.4% [CrI: 1.0%-2.0%] in Maine to 22% [CrI: 18%-27%] in New York. The use of this simple and easy-to-communicate model will improve the ability to make public health decisions that effectively respond to the ongoing pandemic.

  🖺 Full Text HTML: Using Test Positivity and Reported Case Rates to Estimate State-Level COVID-19 Prevalence and Seroprevalence in the United States
• Extensive High-Order Complexes within SARS-CoV-2 Proteome Revealed by Compartmentalization-Aided Interaction Screening -
  Bearing the largest single-stranded RNA genome in nature, SARS-CoV-2 utilizes sophisticated replication/transcription complexes (RTCs), mainly composed of a network of nonstructural proteins and nucleocapsid protein, to establish efficient infection. Here, we developed an innovative interaction screening strategy based on phase separation in cellulo, namely compartmentalization of protein-protein interactions in cells (CoPIC). Utilizing CoPIC screening, we mapped the interaction network among RTC-related viral proteins. We identified a total of 47 binary interactions among 14 proteins governing replication, discontinuous transcription, and translation of coronaviruses. Further exploration via CoPIC led to the discovery of extensive ternary complexes composed of these components, which infer potential higher-order complexes. Taken together, our results present an efficient, and robust interaction screening strategy, and indicate the existence of a complex interaction network among RTC-related factors, thus opening up new opportunities to understand SARS-CoV-2 biology and develop therapeutic interventions for COVID-19.
  🖺 Full Text HTML: Extensive High-Order Complexes within SARS-CoV-2 Proteome Revealed by Compartmentalization-Aided Interaction Screening
• Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2 -
  Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report our efforts to optimize and characterize an HIV-based lentiviral pseudovirus assay for screening neutralizing antibodies for SARS-CoV-2 using a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We assessed different target cells, established conditions that generate readouts over at least a two-log range, and confirmed consistent neutralization titers over a range of pseudovirus input. Using reference sera and plasma panels, we evaluated assay precision and showed that our neutralization titers correlate well with results reported in other assays. Overall, our lentiviral assay is relatively simple, scalable, and suitable for a variety of SARS-CoV-2 entry and neutralization screening assays.
  🖺 Full Text HTML: Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2
• Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay -
  The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates the viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to cell receptor and affect the potency of vaccines and antibodies. Here we used an in-silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay result shows that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit for the development of broadly neutralizing vaccine and antibody.
  🖺 Full Text HTML: Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay
• Unequal but Balanced: Highly educated mothers’ perceptions of work-life balance during the COVID-19 lockdown in Finland and the Netherlands -
  One year after passage of the European work-life balance directive, and thus recognition of the need for policy support, measures to slow the spread of the COVID-19 pandemic are shaping parents’ work-life balance in significant ways. Academically, we are challenged to explore whether existing theoretical frameworks hold in this new environment with combined old and new policy frameworks. We are also challenged to understand the nuanced ways in which the first lockdown affects the combination of paid work and care. We address both of these issues, providing a cross-sectional comparative analysis of highly educated mothers’ perceptions of work-life balance during the COVID-19 pandemic in Finland and the Netherlands. Our findings show that highly educated Finnish mothers have more difficulty combining work and care during the first lockdown than Dutch mothers. The absence of state-provided care during the lockdown creates greater difficulty for full-time working Finnish mothers in a dual-earner/state-carer system than an absence of such care in the Dutch one-and-a-half earner system, where most mothers work part-time. Further analyses suggest variation in part-time and (nearly) full-time hours mitigates the work-life balance experiences of highly educated Dutch mothers. We discuss these findings in light of current theoretical frameworks and highlight avenues for future research.
  🖺 Full Text HTML: Unequal but Balanced: Highly educated mothers’ perceptions of work-life balance during the COVID-19 lockdown in Finland and the Netherlands
• 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

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