Covid-19 Sentry

Contents

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

From Preprints

• Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants -

  The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (67%) serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

  🖺 Full Text HTML: Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants
• A Second Wave? What Do People Mean By COVID Waves? - A Working Definition of Epidemic Waves -

  Policymakers and researchers describe the COVID-19 epidemics by waves without a common vocabulary on what constitutes an epidemic wave, either in terms of a working definition or operationalization, causing inconsistencies and confusions. A working definition and operationalization can be helpful to characterize and communicate about epidemics. We propose a working definition of epidemic waves in the ongoing COVID-19 pandemic and an operationalization based on the public data of the effective reproduction number R. Our operationalization characterizes the numbers and durations of waves (upward and downward) in 178 countries and reveals patterns that can enable healthcare organizations and policymakers to make better description and assessment of the COVID crisis to make more informed resource planning, mobilization, and allocation temporally in the continued COVID-19 pandemic.

  🖺 Full Text HTML: A Second Wave? What Do People Mean By COVID Waves? - A Working Definition of Epidemic Waves
• Antigen-based rapid diagnostic testing or alternatives for diagnosis of symptomatic COVID-19: A simulation-based net benefit analysis -

  Background: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDT) offer the ability to diagnose COVID-19 rapidly and at low cost; however, lower sensitivity than nucleic acid amplification tests (NAAT) has limited adoption of Ag-RDT in clinical settings. Methods: We compared Ag-RDT, NAAT, and clinical judgment alone for diagnosing COVID-19 among symptomatic patients. We considered two scenarios: a high-prevalence hospital setting with 24-hour NAAT turnaround, and a lower-prevalence outpatient setting with 3-day NAAT turnaround. We simulated transmission from cases and contacts and relationships between time, viral burden, transmission, and case detection. We used decision curve analysis to compare the net benefit of diagnostic approaches relying on Ag-RDT versus NAAT. Results: Greater net benefit was achieved with Ag-RDT than NAAT in the outpatient setting, as long as NAAT turnaround time was longer than one day. NAAT was predicted to offer greater net benefit than Ag-RDT in the hospital setting, unless NAAT turnaround times exceeded 2 days. Findings were robust to data-consistent variation in Ag-RDT performance, empiric isolation practices, duration of symptoms, and other model parameters. Both tests provided greater benefit than management based on clinical judgment alone, unless the available interventions carried minimal harm and could be provided at full intensity to all patients in whom COVID-19 diagnosis was considered. Conclusions: Ag-RDT may provide greater net benefit than NAAT for diagnosis of symptomatic COVID-19 in outpatient settings when NAAT turnaround times are longer than one day. NAAT is likely the optimal testing strategy for hospitalized patients, especially those with prolonged symptoms prior to admission.

  🖺 Full Text HTML: Antigen-based rapid diagnostic testing or alternatives for diagnosis of symptomatic COVID-19: A simulation-based net benefit analysis
• On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials -

  Understandably, the recent trials for COVID-19 vaccines have garnered a considerable amount of attention and (as of this writing) vaccinations are about to begin. The popular summaries give infection rates in the vaccinated and placebo and estimated efficacy, which for the two trials we focus on (Moderna and Pfizer) are both near 95%. This paper explores the potential effects of possible false positives or false negatives (misclassification) in the COVID-19 diagnosis with specific application to the Moderna and Pfizer trials. The general conclusion, fortunately, is that these potential misclassifications almost always would lead to underestimation of the efficacy and that correcting for false positives or negatives will lead to even higher estimated efficacy.

  🖺 Full Text HTML: On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials
• Bored by bothering: A cost-value approach to pandemic boredom -
  In an effort to mitigate the impact of the COVID-19 pandemic, countries around the world have employed non-pharmaceutical containment measures. The effectiveness of such mitigation efforts relies on individual compliance (e.g., avoiding to travel or to gather). Crucially, adhering to the required behavioral recommendations places substantial burdens on those who are asked to follow them. One particularly likely outcome of adherence should be the experience of boredom. Thus, people might get bored by bothering. Drawing from research and theorizing on reward-based decision making, we conducted a high-powered study (N = 1553 US participants) to investigate whether the value and effort people ascribe to adherence to containment measures directly and indirectly (i.e., mediated by adherence) affects their experience of boredom. As expected, structural equation modeling revealed that high value and low effort predicted compliance with behavioral recommendations. Moreover, higher compliance was linked to more boredom, meaning that high value and low effort increased boredom via compliance. In contrast, high value and low effort had direct effects on boredom in the opposite direction (i.e., decreasing boredom). Attesting to their robustness and generalizability, these findings held for both prospective (with respect to upcoming winter holidays) and retrospective behavior (with respect to previous thanksgiving holidays), across US states which had or had not enforced behavioral restrictions, individual differences in boredom proneness, and demographic variables. Taken together, our results show that people can indeed get bored by bothering: Complying with nonpharmacological containment measures like avoiding to travel and to gather can come at the cost of getting bored, an experience that was strongly linked to negative affect in our study. While the observed levels of compliance were relatively high and those of boredom were relatively low, the data suggest that this could change over time because levels of boredom might rise. This might render maintenance of compliance in the general public increasingly difficult. However, we illustrate how policy makers can rely on theoretical models of boredom and behavior to maintain compliance and discuss the chances and pitfalls of doing so.
  🖺 Full Text HTML: Bored by bothering: A cost-value approach to pandemic boredom
• An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2 -
  The on-going coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has infected hundreds of millions of people and killed more than two million people worldwide. Currently, there are no effective drugs available for treating SARS-CoV-2 infections; however, vaccines are now being administered worldwide to control this virus. In this study, we have studied SARS-CoV-2 helicase, Nsp13, which is critical for viral replication. We compared the Nsp13 sequences reported from India with the first reported sequence from Wuhan province, China to identify and characterize the mutations occurring in this protein. To correlate the functional impact of these mutations, we characterised the most prominent B cell and T cell epitopes contributed by Nsp13. Our data revealed twenty-one epitopes, which exhibited high antigenicity, stability and interactions with MHC class-I and class-II molecules. Subsequently, the physiochemical properties of these epitopes were also analysed. Furthermore, several of these Nsp13 epitopes harbour mutations, which were further characterised by secondary structure and per-residue disorderness, stability and dynamicity predictions. Altogether, we report the candidate epitopes of Nsp13 that may help the scientific community to understand the evolution of SARS-CoV-2 variants and their probable implications.
  🖺 Full Text HTML: An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2
• Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors -
  SARS-CoV-2 infection initiates with the attachment of spike protein to the ACE2 receptor. While vaccines have been developed, no SARS-CoV-2 specific small molecule inhibitors have been approved. Herein, utilizing the crystal structure of the ACE2/Spike receptor binding domain (S-RBD) complex in computer-aided drug design (CADD) approach, we docked ~8 million compounds within the pockets residing at S-RBD/ACE2 interface. Five best hits depending on the docking score, were selected and tested for their in vitro efficacy to block SARS-CoV-2 replication. Of these, two compounds (MU-UNMC-1 and MU-UNMC-2) blocked SARS-CoV-2 replication at sub-micromolar IC50 in human bronchial epithelial cells (UNCN1T) and Vero cells. Furthermore, MU-UNMC-2 was highly potent in blocking the virus entry by using pseudoviral particles expressing SARS-CoV-2 spike. Finally, we found that MU-UNMC-2 is highly synergistic with remdesivir (RDV), suggesting that minimal amounts are needed when used in combination with RDV, and has the potential to develop as a potential entry inhibitor for COVID-19.
  🖺 Full Text HTML: Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors
• SARS-CoV-2 B.1.1.7 infection of Syrian hamster does not cause more severe disease and is protected by naturally acquired immunity -
  Epidemiological studies have revealed the emergence of multiple SARS-CoV-2 variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and re-infection studies in naive and convalescent Syrian hamsters (>10 months old). Hamsters infected by either a B.1.1.7 variant or a B.1 (G614) variant exhibited comparable viral loads and pathology. Convalescent hamsters that were previously infected by the original D614 variant were protected from disease following B.1.1.7 challenge with no observable clinical signs or lung pathology. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in hamsters and that natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant.
  🖺 Full Text HTML: SARS-CoV-2 B.1.1.7 infection of Syrian hamster does not cause more severe disease and is protected by naturally acquired immunity
• Observational study of changes in utilization and outcomes in non-invasive ventilation in COVID-19 -

  Rationale The role of non-invasive ventilation (NIV) in severe COVID-19 remains a matter of debate. Objectives To determine the utilization and outcome of NIV in COVID-19 in an unbiased cohort. Methods Observational study of confirmed COVID19 cases of claims data of the Local Health Care Funds comparing patients with non-invasive and invasive mechanical ventilation (IMV) between spring versus autumn period 2020. Measurements and Main Results: Nationwide cohort of 7490 cases (median/IQR age 70/60 to 79 years, 66% male) 3851 (51%) patients primarily received IMV without NIV, 1614 (22%) patients received NIV without subsequent intubation, and 1247 (17%) patients had NIV failure (NIV F), defined by subsequent endotracheal intubation. The proportion of patients who received invasive MV decreased from 74% to 39% during the second period. Accordingly, the proportion of patients with NIV exclusively increased from 10% to 28%, and those failing NIV increased from 9% to 21%. Median length of hospital stay decreased from 26 to 22 days, and duration of MV decreased from 11.6 to 7.6 days. The NIV failure rate decreased from 49% to 42%. Overall mortality remained unchanged (51% versus 53%). Mortality was 39% with NIV-only, 52% with IMV and 66% with NIV-F with mortality rates steadily increasing from 58% in early NIV F (day 1) to 75% in late NIV F (>4 days). Conclusion: Utilization of NIV rapidly increased during the autumn period, which was associated with a reduced duration of MV, but not with overall mortality. High NIV F rates are associated with increased mortality, particularly in late NIV F.

  🖺 Full Text HTML: Observational study of changes in utilization and outcomes in non-invasive ventilation in COVID-19
• A high-throughput fluorescence polarization assay to discover inhibitors of arenavirus and coronavirus exoribonucleases -
  Viral exoribonucleases are uncommon in the world of RNA viruses. To date, this activity has been identified only in the Arenaviridae and the Coronaviridae families. These exoribonucleases play important but different roles in both families: for mammarenaviruses the exoribonuclease is involved in the suppression of the host immune response whereas for coronaviruses, exoribonuclease is both involved in a proofreading mechanism ensuring the genetic stability of viral genomes and participating to evasion of the host innate immunity. Because of their key roles, they constitute attractive targets for drug development. Here we present a high-throughput assay using fluorescence polarization to assess the viral exoribonuclease activity and its inhibition. We validate the assay using three different viral enzymes from SARS-CoV-2, lymphocytic choriomeningitis and Machupo viruses. The method is sensitive, robust, amenable to miniaturization (384 well plates) and allowed us to validate the proof-of-concept of the assay by screening a small focused compounds library (23 metal chelators). We also determined the IC50 of one inhibitor common to the three viruses.
  🖺 Full Text HTML: A high-throughput fluorescence polarization assay to discover inhibitors of arenavirus and coronavirus exoribonucleases
• Transformations, Lineage Comparisons, and Analysis of Down to Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein Including the UK Variant B.1.1.7 -
  Monitoring and strategic response to variants in SARS-CoV-2 represents a considerable challenge in the current pandemic, as well as potentially future viral outbreaks of similar magnitude. In particular mutations and deletions involving the virion’s prefusion Spike protein have significant potential impact on vaccines and therapeutics that utilize this key structural viral protein in their mitigation strategies. In this study, we have demonstrated how dominant energetic landscape mappings (“glue points”) coupled with sequence alignment information can potentially identify or flag key residue mutations and deletions associated with variants. Surprisingly, we also found excellent homology of stabilizing residue glue points across the lineage of {beta} coronavirus Spike proteins, and we have termed this as “sequence homologous glue points”. In general, these flagged residue mutations and/or deletions are then computationally studied in detail using all-atom biocomputational molecular dynamics over approximately one microsecond in order to ascertain structural and energetic changes in the Spike protein associated variants. Specifically, we examined both a theoretically-based triple mutant and the so-called UK or B.1.1.7 variant. For the theoretical triple mutant, we demonstrated through Alanine mutations, which help “unglue” key residue-residue interactions, that these three key stabilizing residues could cause the transition of Down to Up protomer states, where the Up protomer state allows binding of the prefusion Spike protein to hACE2 host cell receptors, whereas the Down state is believed inaccessible. Thus, we are able to demonstrate the importance of glue point residue identification in the overall stability of the prefusion Spike protein. For the B.1.1.7 variant, we demonstrated the critical importance of D614G and N5017 on the structure and binding, respectively, of the Spike protein. Notably, we had previously identified D614 as a key glue point in the inter-protomer stabilization of the Spike protein prior to the emergence of its mutation. The mutant D614G is a structure breaking Glycine mutation demonstrating a relatively more distal Down state RBD and a more stable conformation in general. In addition, we demonstrate that the mutation N501Y may significantly increase the Spike protein binding to hACE2 cell receptors through its interaction with Y41 of hACE2 forming a potentially strong hydrophobic residue binding pair. We note that these two key mutations, D614G and N501Y, are also found in the so-called South African (SA; B.1.351) variant of SARS-CoV-2. Future studies along these lines are, therefore, aimed at mapping glue points to residue mutations and deletions of associated prefusion Spike protein variants in order to help identify and analyze possible “variants of interest” and optimize efforts aimed at the mitigation of this current and future virions.
  🖺 Full Text HTML: Transformations, Lineage Comparisons, and Analysis of Down to Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein Including the UK Variant B.1.1.7
• Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors -

  Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma is likely to reflect the antigenic composition of local viral strains, we hypothesized that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to a national registry of hospitalized COVID-19 patients supported this hypothesis. These findings have implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

  🖺 Full Text HTML: Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors
• Quantifying the Benefits of Targeting for Pandemic Response -

  To respond to pandemics such as COVID-19, policy makers have relied on interventions that target specific population groups or activities. Such targeting is potentially contentious, so rigorously quantifying its benefits and downsides is critical for designing effective and equitable pandemic control policies. We propose a flexible modeling framework and a set of associated algorithms that compute optimally targeted, time-dependent interventions that coordinate across two dimensions of heterogeneity: population group characteristics and the specific activities that individuals engage in during the normal course of a day. We showcase a complete implementation in a case study focused on the Île-de-France region of France, based on commonly available hospitalization, community mobility, social contacts and economic data. We find that optimized dual-targeted policies have a simple and explainable structure, imposing less confinement on group-activity pairs that generate a relatively high economic value prorated by activity-specific social contacts. When compared to confinements based on uniform or less granular targeting, dual-targeted policies generate substantial complementarities that lead to Pareto improvements, reducing the number of deaths and the economic losses overall and reducing the time in confinement foreach population group. Since dual-targeted policies could lead to increased discrepancies in the confinements faced by distinct groups, we also quantify the impact of requirements that explicitly limit such disparities, and find that satisfactory intermediate trade-offs may be achievable through limited targeting.

  🖺 Full Text HTML: Quantifying the Benefits of Targeting for Pandemic Response
• The role of connectivity on COVID-19 preventive approaches -

  Preventive and modelling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of the population contact structure and individual connectivity. To address this gap, we developed models that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such vaccination approaches. We conclude that the most effective vaccination strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions.

  🖺 Full Text HTML: The role of connectivity on COVID-19 preventive approaches
• A realistic touch-transfer method reveals low risk of transmission for SARS-CoV-2 by contaminated coins and bank notes -
  The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.
  🖺 Full Text HTML: A realistic touch-transfer method reveals low risk of transmission for SARS-CoV-2 by contaminated coins and bank notes

From Clinical Trials

• Neuromodulation in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Device: Transcranial direct-current stimulation;   Device: Sham Transcranial direct-current stimulation
  Sponsors:   D’Or Institute for Research and Education;   Rio de Janeiro State Research Supporting Foundation (FAPERJ);   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition:   COVID-19
  Interventions:   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd
  Recruiting

• Efficacy, Immunogenicity and Safety of Inactivated ERUCOV-VAC Compared With Placebo in COVID-19 - Condition:   COVID-19
  Interventions:   Biological: ERUCOV-VAC 3 µg/0.5 ml Vaccine;   Biological: ERUCOV-VAC 6 µg/0.5 ml Vaccine;   Other: Placebo
  Sponsors:   Health Institutes of Turkey;   Erciyes University Scientific Research Projects Coordination
  Recruiting

• ANTIcoagulation in Severe COVID-19 Patients - Condition:   Severe COVID-19 Pneumonia
  Interventions:   Drug: Tinzaparin, Low dose prophylactic anticoagulation;   Drug: Tinzaparin, High dose prophylactic anticoagulation;   Drug: Tinzaparin,Therapeutic anticoagulation
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• The Effects of Web-Based Training for Covid-19 Patients on Symptom Management, Medication Compliance and Quality of Life - Condition:   COVID-19
  Intervention:   Other: intervention group
  Sponsor:   Eskisehir Osmangazi University
  Not yet recruiting

• A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ensovibep;   Drug: Placebo
  Sponsors:   Molecular Partners AG;   Novartis Pharmaceuticals;   Iqvia Pty Ltd;   Datamap;   SYNLAB Analytics & Services Switzerland AG;   Q2 Solutions
  Not yet recruiting

• A Study to Test BI 767551 in People With Mild to Moderate Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: BI 767551 intravenous;   Drug: BI 767551 inhaled;   Drug: Placebo intravenous;   Drug: Placebo inhaled
  Sponsor:   Boehringer Ingelheim
  Not yet recruiting

• Tele-rehabilitation Program After Hospitalization for COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Other: TR;   Other: TSu
  Sponsors:   Istituti Clinici Scientifici Maugeri SpA;   Istituto Auxologico Italiano
  Recruiting

• ENO Breathe vs Usual Care in COVID-19 Recovery: An RCT - Condition:   COVID-19 Recovery
  Intervention:   Other: ENO Breathe group
  Sponsors:   Imperial College London;   Imperial College Healthcare NHS Trust
  Not yet recruiting

• Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Xuanfei Baidu Granules;   Other: Placebo
  Sponsor:   Darcy Spicer
  Recruiting

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Lyophilized Formulation of BNT162b2 Against COVID-19 in Healthy Adults - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Biological: BNT162b2
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition:   Covid19
  Intervention:   Diagnostic Test: Anti-SARS-CoV2 Serology
  Sponsor:   Université de Reims Champagne-Ardenne
  Completed

• Assessment of the Impact of Oral Intervention With Cetylpyridinium Chloride to Decrease SARS-CoV-2 Viral Load in Patients With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Other: ORAL INTERVENTION WITH CETYLPYRIDINIUM CHLORIDE;   Other: PLACEBO
  Sponsors:   Rosa Tarrago;   Dentaid SL
  Recruiting

• Study of DS-5670a (COVID-19 Vaccine) in Japanese Healthy Adults and Elderly Subjects - Condition:   Covid19
  Interventions:   Biological: DS-5670a;   Biological: Placebo
  Sponsor:   Daiichi Sankyo Co., Ltd.
  Recruiting

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children <12 Years of Age - Condition:   SARS-CoV-2 Infection, COVID-19
  Interventions:   Biological: Biological/Vaccine: BNT162b2 10mcg;   Biological: BNT162b2 20mcg;   Biological: BNT162b2 30mcg
  Sponsors:   BioNTech SE;   Pfizer
  Recruiting

From PubMed

• Effectiveness of Azithromycin as add-on Therapy in COVID-19 Management - As winter is knocking the door, the risk of respiratory tract infection is increasing at present scenario due to no prophylaxis of Covid-19. So, no one is safe until everyone is safe. Worldwide researchers are looking for the vaccine to remove the need for social distancing, mask-wearing and social gathering. A vaccine is like many other outcomes if the vaccine would be available; we cannot say about the effectiveness of the vaccine. Several drugs are testing to save the people life from…

• COVID19-inhibitory activity of withanolides involves targeting of the host cell surface receptor ACE2: insights from computational and biochemical assays - SARS-CoV-2 outbreak in China in December 2019 and its spread as worldwide pandemic has been a major global health crisis. Extremely high infection and mortality rate has severely affected all sectors of life and derailed the global economy. While drug and vaccine development have been prioritized and have made significant progression, use of phytochemicals and herbal constituents is deemed as a low-cost, safer and readily available alternative. We investigated therapeutic efficacy of eight…

• Low-Cost and Scalable Platform with Multiplexed Microwell Array Biochip for Rapid Diagnosis of COVID-19 - Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction…

• Tocilizumab and PMX-DHP have efficacy for severe COVID-19 pneumonia - In coronavirus disease 2019 pneumonia, a cytokine storm resulting from an excessive inflammatory response to the viral infection is thought to play a role in the exacerbation of the pneumonia and its prognosis. Favipiravir and ciclesonide are not effective in the inhibition of the cytokine storm. In this case report, we describe the experience of tocilizumab administration and polymyxin B immobilized fiber direct hemoperfusion in severe coronavirus disease 2019 pneumonia patient. A 52-year-old…

• Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2 - In a cohort of BNT162b2 (Pfizer-BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar…

• A review on antiviral and immunomodulatory polysaccharides from Indian medicinal plants, which may be beneficial to COVID-19 infected patients - The emergence of the novel coronavirus, SARS-CoV-2 has pushed forward the world to experience the first pandemic of this century. Any specific drug against this RNA virus is yet to be discovered and presently, the COVID-19 infected patients are being treated symptomatically. During the last few decades, a number of polysaccharides with potential biological activities have been invented from Indian medicinal plants. Many polysaccharides, such as sulfated xylomannan, xylan, pectins, fucoidans,…

• SARS-CoV2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential - Coronaviruses have caused multiple epidemics in the past two decades, in addition to the current COVID-19 pandemic that is severely damaging global health and the economy. Coronaviruses employ between twenty and thirty proteins to carry out their viral replication cycle including infection, immune evasion, and replication. Among these, nonstructural protein 16 (Nsp16), a 2’-O-methyltransferase, plays an essential role in immune evasion. Nsp16 achieves this by mimicking its human homolog, CMTr1,…

• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies - The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of all…

• Weak humoral immune reactivity among residents of long-term care facilities following one dose of the BNT162b2 mRNA COVID-19 vaccine - BACKGROUND: Several Canadian provinces are extending the interval between COVID-19 vaccine doses to increase population vaccine coverage more rapidly. However, immunogenicity of these vaccines after one dose is incompletely characterized, particularly among the elderly, who are at greatest risk of severe COVID-19.

• Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19 - COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19, that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of Granulocytic-MDSC (G-MDSC) may in part explain…

• Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous…

• TMPRSS2 inhibitor discovery facilitated through an in silico and biochemical screening platform - The COVID-19 pandemic has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a highly promising antiviral target, as it plays a direct role in priming the spike protein before viral entry occurs. Further, unlike other targets such as ACE2, TMPRSS2 has no known biological role. Here we utilize virtual screening to curate large libraries into a…

• The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection - We identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone ¹ , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications ² , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry ³ . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone…

• BTK inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review - ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched…

• Tocilizumab: An Effective Therapy for Severely and Critically Ill COVID-19 Patients - Background: Tocilizumab (TCZ), a monoclonal antibody against the most prevalent cytokine interleukin-6 (IL-6), is an emerging therapeutic option for COVID-19 infections. The present study was undertaken to assess the therapeutic response of TCZ therapy in severely or critically ill COVID-19 patients and its role as an effective modality of management. Methods: The present retrospective observational study included 30 admitted severely or critically ill COVID-19 patients, treated with TCZ therapy…

From Patent Search

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link

• IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link

• Aronia-Mundspray -

  Anordnung zum Versprühen einer Substanz in die menschliche Mundhöhle und/oder in den Rachen oder zum Trinken, dadurch gekennzeichnet, dass die Anordnung eine Flasche mit einer Substanz aufweist, die wenigstens Aroniasaft und eine Alkoholkomponente aufweist und einen Sprühkopf besitzt.

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• 一种用于检测新型冠状病毒COVID-19的引物组及试剂盒 - 本发明涉及生物技术领域，特别是涉及一种用于检测冠状病毒的引物组及试剂盒，所述引物组包括以下中的一对或多对：外侧引物对：所述外侧引物对包括如SEQ ID NO:1所示的上游引物F3和如SEQ ID NO:2所示的下游引物B3；内侧引物对：所述内侧引物对包括如SEQ ID NO:3所示的上游引物FIP和如SEQ ID NO:4所示的下游引物BIP；环引物对：所述环引物对包括如SEQ ID NO:5所示的上游引物LF和如SEQ ID NO:6所示的下游引物LB。试剂盒包括所述引物组。本发明在一个管中整合了RT‑LAMP和CRISPR，能依据两次颜色变化检测病毒和各种靶标核酸。 - link

• 新冠病毒中和性抗体检测试剂盒 - 本发明提供一种新冠病毒中和性抗体检测试剂盒。所述试剂盒基于BAS‑HTRF技术，主要包含：生物素标记的hACE2、新冠病毒棘突蛋白RBD‑Tag1、能量供体Streptavidin‑Eu cryptate、能量受体MAb Anti‑Tag1‑d2和新冠病毒中和性抗体。本发明将BAS和HTRF两种技术相结合，用于筛选新型冠状病毒中和性抗体，3小时内即可实现筛选，且操作简单，无需经过多次洗板过程。BAS和HTRF联用大大提升了反应灵敏度，且两种体系都能最大限度地减少非特异的干扰，适用于血清样品的检测。该方法可实现高通量检测，对解决大批量样品的新冠病毒中和性抗体的检测具有重要意义。 - link

• Infektionsschutzmaske -

  Infektionsschutzmaske (1) zum Schutz vor Übertragung von Infektionskrankheiten mit einer Außen - und einer Innenseite (2,3) sowie Haltemitteln (5) zum Befestigen der Infektionsschutzmaske (1) am Kopf eines Maskenträgers, dadurch gekennzeichnet, dass an der Infektionsschutzmaske (1) mindestens eine Testoberfläche (6) zum Nachweis von Auslösern einer Infektionskrankheit derart angeordnet ist, dass diese bei korrekt angelegter Infektionsschutzmaske (1) mit der Ausatemluft des Maskenträgers unmittelbar in Kontakt gelangt.

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• Sars-CoV-2 vaccine antigens - - link