Covid-19 Sentry

Contents

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

From Preprints

• Recent changes in COVID-19 Vaccine Hesitancy among Healthcare Workers -

  Introduction. Early COVID-19 vaccine acceptance rates suggest that up to one-third of HCWs may be vaccine-hesitant. However, it is unclear whether hesitancy among HCWs has improved with time and if there are temporal changes whether these differ by healthcare worker role. Methods. In October 2020, a brief survey was sent to all participants in the Healthcare Worker Exposure Response and Outcomes (HERO) Registry with a yes/no question regarding vaccination under emergency use authorization (EUA): “If an FDA emergency use-approved vaccine to prevent coronavirus/COVID-19 was available right now at no cost, would you agree to be vaccinated?” The poll was repeated in December 2020, with the same question sent to all registry participants. Willingness was defined as a “Yes” response, and hesitancy was defined as a “No” response. Participants were stratified into clinical care roles. Baseline demographics of survey respondents at each timepoint were compared using appropriate univariate statistics (chi-squared and t-tests). Analyses were descriptive, with frequencies and percentages reported for each category. Results. Of 4882 HERO active registry participants during September 1-October 31, 2020, 2070 (42.4%) completed the October survey, and n=1541 (31.6%) completed the December survey. 70.2% and 67.7% who were in clinical care roles, respectively. In October, 54.2% of HCWs in clinical roles said they would take an EUA-approved vaccine, which increased to 76.2% in December. The largest gain in vaccine willingness was observed among physicians, 64.0% of whom said they would take a vaccine in October, compared with 90.5% in December. Nurses were the least likely to report that they would take a vaccine in both October (46.6%) and December (66.9%). We saw no statistically significant differences in age, race/ethnicity, gender, or medical role between time points. When restricting to the 998 participants who participated at both time points, 69% were vaccine-willing at both time points; 15% were hesitant at both time points, 13% who were hesitant in October were willing in December; and 2.9% who were willing in October were hesitant in December. Conclusions. In a set of cross-sectional surveys of vaccine acceptance among healthcare workers, willingness improved substantially over 2 calendar months during which the US had a presidential election and two vaccine manufacturers released top-line Phase 3 trial results. While improved willingness was observed in all role categories, nurses reported the most vaccine hesitancy at both time points.

  🖺 Full Text HTML: Recent changes in COVID-19 Vaccine Hesitancy among Healthcare Workers
• Accounting for health inequities in the design of contact tracing interventions: a rapid review -

  Context: Contact tracing has been a central COVID-19 transmission control measure. However, without the consideration of the needs of specific populations, public health interventions can exacerbate health inequities. Purpose: The purpose of this rapid review was to determine if and how health inequities were included in the design of contact tracing interventions in epidemic settings. Method: We conducted a search of the electronic databases MEDLINE and Web of Science. Our inclusion criteria included articles that: (i) described the design of contact tracing interventions, (ii) have been published between 2013 and 2020 in English, French, Spanish, Chinese, or Portuguese, (iii) and included at least 50% of empiricism, according to the Automated Classifier of Texts on Scientific Studies (ATCER) tool. We relied on various tools to extract data. Result: Following the titles and abstracts screening of 230 articles, 39 articles met the inclusion criteria. Only seven references were retained after full text review. None of the selected studies considered health inequities in the design of contact tracing interventions. Conclusion: The use of tools/concepts for incorporating health inequities, such as the REFLEX-ISS tool, and 9proportionate universalism9 when designing contact tracing interventions, would enable practitioners, decision makers, and researchers to better consider health inequities.

  🖺 Full Text HTML: Accounting for health inequities in the design of contact tracing interventions: a rapid review
• Efficacy of AYUSH 64 as add-on therapy in early stage COVID 19 - An open-label randomized controlled pilot study -
  Background: Efficacy of AYUSH 64 has been proven in fever and influenza-like illness earlier. Hence it was felt it should be evaluated in COVID 19 which has similar symptom complex. Aim: To evaluate the clinical efficacy of AYUSH 64 as an add-on to standard care in early stage COVID-19 patients. Materials and methods: After obtaining IEC permission, a single centre, randomized, open labelled, controlled, pilot study was undertaken. Asymptomatic to mild COVID 19 (RT-PCR positive) patients, who gave written informed consent, were randomly allotted either AYUSH 64 for 14 days as an add-on treatment to standard care or standalone standard care. The outcomes variables were changes in WHO ordinal scale for clinical improvement, incidence of development of COVID symptoms, use of oxygen therapy, use of mechanical ventilator, duration of total symptomatic phase, adverse drug reaction, death and changes in laboratory values. Results: Among total 115 screened, 80 participants were included, out of which 41 received AYUSH 64 in addition to standard care and 39 only standard care. The mean final WHO score was comparable for both the Groups, however, mean scores in the interventional Group showed downward trend from 7th day onwards as compared to the control Group. Difference in laboratory values and need for oxygen were not statistically significant in both the Groups. No incidence of the requirement of a mechanical ventilator, adverse drug reaction, and death were observed in either of the Groups. Conclusion: The findings of this study show that an integrated approach of AYUSH 64 with standard care did not exert promising difference in core outcomes of COVID-19 when compare to standalone standard care. However, a trend towards lower values was observed in the symptoms in AYUSH 64 add-on group in comparison to standalone standard care.
  🖺 Full Text HTML: Efficacy of AYUSH 64 as add-on therapy in early stage COVID 19 - An open-label randomized controlled pilot study
• Add-on Ayurveda Treatment for early stage COVID-19: A single centre retrospective cohort study from Gujarat, India -
  The retrospective cohort study aimed to evaluate the clinical outcomes of Ayurveda treatment exposure as an add-on to conventional care in early stage COVID-19 patients admitted at Samaras COVID care centre, Ahmedabad, India. Conventional care included Vitamin-c, Azithromycin, and Paracetamol. Ayurveda formulations used as add-on were Dashamula and Pathyadi decoctions along with Trikatu powder, Sanshamani tablet, AYUSH -64 tablet AND Yastimadhu Ghana tablet for oral administration. Considering Add-on Ayurveda medicines as exposure of interest, patients who received Add-on Ayurveda medicines at least for seven days were included in the exposed group while those who received only conventional care in unexposed group. Data was collected through record review and telephonic interviews. The outcomes of interest were the development of symptoms, duration of symptomatic phase in those progressing to symptomatic stage and mortality. Total 762 participants were included [541 (71%) in the exposed group and 221 (29%) in the unexposed]. Progression to symptomatic phase did not differ significantly between groups [27.6 % in exposed, 24.6% in unexposed, adjusted RR 0.85; 95% CI 0.6-1.2]. The total duration of symptomatic phase among those progressing to the symptomatic stage was significantly decreased in the exposed group (x̅= 3.66±1.55 days in exposed (n=133); x̅= 5.34±3.35 days in unexposed (n=61), p<0.001). No mortality was observed in either of the groups. Ayurveda Treatment as adjunctive to conventional care reduced the duration of symptomatic phase in early stage COVID 19 as compared to standalone conventional care. Add-on Ayurveda treatment has promising potential for management of early stage COVID-19.
  🖺 Full Text HTML: Add-on Ayurveda Treatment for early stage COVID-19: A single centre retrospective cohort study from Gujarat, India
• Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay -

  Background: The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the in vitro quantitative detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the performance of this assay using samples from seven sites in Germany, Austria, and Switzerland. Methods: Anonymized frozen, residual serum, or plasma samples from blood donation centers or routine diagnostic testing were used for this study. For specificity and sensitivity analyses, presumed negative samples collected before October 2019 and SARS-CoV-2 PCR-confirmed single or sequential samples were tested, respectively. The performance of the Elecsys Anti-SARS-CoV-2 S immunoassay was also compared with other commercial immunoassays. Results: The overall specificity (n=7880 pre-pandemic samples) and sensitivity (n=240 PCR-positive samples [≥14 days post-PCR]) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87–99.99) and 97.92% (95% CI: 95.21–99.32), respectively. Compared with seven other immunoassays, the Elecsys Anti-SARS-CoV-2 S assay had comparable or greater specificity and sensitivity. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG, ADVIA Centaur® SARS-CoV-2 Total, ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG and IgA assays, and significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgG and IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG assays. Conclusion: The Elecsys Anti-SARS-CoV-2 S assay demonstrated a robust and favorable performance across samples from multiple European sites, with a very high specificity and sensitivity for the detection of anti-S antibodies.

  🖺 Full Text HTML: Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay
• Cytoplasmic domain and enzymatic activity of ACE2 is not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells -
  The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor- human angiotensin converting enzyme 2 (ACE2). Here, we used lentivirus based pseudotypes bearing spike protein to demonstrate that entry of SARS-CoV-2 into host cells is dependent on clathrin-mediated endocytosis, and phosphoinositides play essential role during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 is not required for efficient virus entry. These results provide new insights into SARS-CoV-2 cellular entry and present potential targets for drug development.
  🖺 Full Text HTML: Cytoplasmic domain and enzymatic activity of ACE2 is not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells
• Natural Selection as the Sum over all Histories and a Differential Equation for Environmental Coevolution. -
  As evolution can be connected to the principle of least action, and if it is depicted in evolution-space versus time then it corresponds to the direction of ultimate causation. As an organism evolves and follows a path of proximate causation, if the vector is closely parallel to that of the Ultimate Causation then the changes will confer desirable attributes which will lead to further development. If, however, the variations do not occur in a direction close to that of the ultimate causation vector the evolved organism will quickly die out. This may be viewed as similar to Feynmans sum over all histories. Therefore, the principle of least action gives a direction, but not a purpose, to evolution. Taking the coevolution model of Lewontin, an equation of motion for environmental coevolution shows that it is the rate of evolutionary change that responds to changes in the environment. Unfortunately, it is not possible to compare the theory with viral or bacterial mutation rates, as these are not measured on a time base. However, there is some preliminary evidence from recent Covid-19 studies that the model maybe correct. There is positive evidence from population level avian studies. Further analysis shows that the rate of change of the coefficient of additive evolvability (Cav) and its square ( IA) with environmental favourability are linear, which could help in defining the Lagrangian of the environmental effects. However, this is potentially bad news for Covid-19 as. although the data is not yet available, as the stress on the environment for the virus increases due to the vaccination programme, then the mutation rate will increase, and we are in a continual catch-up scenario as with the influenza virus.
  🖺 Full Text HTML: Natural Selection as the Sum over all Histories and a Differential Equation for Environmental Coevolution.
• Investigation of ventilation conditions associated with CO2 concentration changes in ultrasonographic exam room from the perspective of COVID-19 infection control -

  Objectives Ventilation is an important factor in preventing COVID-19 infection. To clarify the state of ventilation in ultrasonic exam rooms, as an index of ventilation rate, the carbon dioxide (CO2) concentration in our exam rooms was measured. Methods We measured the CO2 concentration in each exam room before the examination and 0-15 minutes after end of the exam. The subjects were 70 cases (abdomen: 24, breast: 16, neck: 16, and musculoskeletal: 14). In infant cases, one parent accompanied the patient during the examination. Results The highest CO2 concentration was 2261 ppm, observed after the breast examination. In all cases, the CO2 concentration in the exam room was highest immediately after the examination or two minutes after. Almost all cases had recovered to within 120% of the pre-examination CO2 concentrations within 15 minutes after the examination. The average CO2 concentration after ultrasonography was significantly higher for breast examinations than others. Conclusions Even in a hospital with modern ventilation equipment, the CO2 concentration in the ultrasound room was high after the exam and it takes 15 minutes to recover to the pre-exam state. Care must be taken to ensure adequate ventilation in ultrasonographic facilities.

  🖺 Full Text HTML: Investigation of ventilation conditions associated with CO2 concentration changes in ultrasonographic exam room from the perspective of COVID-19 infection control
• High Initial Titres of Anti-Spike Antibodies following SARS-CoV-2 Infection is Associated with Faster Decay Rates at Four Months Follow-Up -

  Background Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggests an initial decay of antibody followed by subsequent stabilization. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCW). Methods In this cross-sectional longitudinal cohort study done in two phases over four months, HCW underwent serial qualitative serology testing for anti-N antibody, quantitative MSH-ELISA to detect Receptor Binding Domain and full-length S reactive antibodies and completed online surveys about COVID-19 related symptoms and healthcare/community exposure. Results Anti-N antibody positivity was 27% and anti-S positivity was 28% in Phase 1. In Phase 2 anti-S titres were higher in symptomatic than in asymptomatic positive subjects in Phase 1. Marginally higher titers were seen in asymptomatic compared to the symptomatic positive subgroup in Phase 2. A positive correlation was noted between age, number and duration of symptoms, and Phase 1 anti-S antibody titre. A strong correlation was observed between Phase 1 titers and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever, GI symptoms, and total number and duration of COVID-19 symptoms. Conclusions Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as faster decay during the two time points.

  🖺 Full Text HTML: High Initial Titres of Anti-Spike Antibodies following SARS-CoV-2 Infection is Associated with Faster Decay Rates at Four Months Follow-Up
• Safety and Immunogenicity Evaluation of Inactivated whole-virus-SARS-COV-2 In Mice As Emerging Vaccine Development In Egypt -
  The current worldwide pandemic COVID-19 is causing severe human health problems, with high numbers of mortality rates and huge economic burdens that require an urgent demand for safe, and effective and vaccine development. Our study was the first trail to development and evaluation of safety and immune response to inactivated whole SARS-COV-2 virus vaccine adjuvanted with aluminium hydroxide. We used characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069 and MW250352 at GenBank that isolated from Egyptian patients SARS-CoV-2-positive. Development of the vaccine was carried out in a BSL - 3 facilities and the immunogenicity was determined in mice at two doses (55ug and 100ug per dose). All vaccinated mice were received a booster dose 14 days post first immunization. Our results demonstrated distinct cytopathic effect on the vero cell monolayers induced through SARS-COV-2 propagation and the viral particles were identified as Coronaviridae by transmission electron microscopy. SARS-CoV-2 was identified by RT-PCR performed on the cell culture. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless the dose concentration, with excellent safety profiles. However, no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by wild virus challenge the vaccinated mice and detection of viral replication in lung tissues. Vaccinated mice recorded complete protection from challenge infection three weeks post second dose. SARS-COV-2 replication was not observed in the lungs of mice following SARS-CoV-2 challenge, regardless of the level of serum neutralizing antibodies. This finding will support the future trials for evaluation an applicable SARS-CoV-2 vaccine candidate.
  🖺 Full Text HTML: Safety and Immunogenicity Evaluation of Inactivated whole-virus-SARS-COV-2 In Mice As Emerging Vaccine Development In Egypt
• Fragment-based computational design of antibodies targeting structured epitopes -
  De novo design methods hold the promise of reducing the time and cost of antibody discovery, while enabling the facile and precise targeting of specific epitopes. Here we describe a fragment-based method for the combinatorial design of antibody binding loops and their grafting onto antibody scaffolds. We designed and tested six single-domain antibodies targeting different epitopes on three antigens, including the receptor-binding domain of the SARS-CoV-2 spike protein. Biophysical characterisation showed that all designs are highly stable, and bind their intended targets with affinities in the nanomolar range without any in vitro affinity maturation. We further show that a high-resolution input antigen structure is not required, as our method yields similar predictions when the input is a crystal structure or a computer-generated model. This computational procedure, which readily runs on a laptop, provides the starting point for the rapid generation of lead antibodies binding to pre-selected epitopes.
  🖺 Full Text HTML: Fragment-based computational design of antibodies targeting structured epitopes
• High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins -
  Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2,SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e.g., NSP1, Orf6, NSP3, and NSP5) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.
  🖺 Full Text HTML: High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins
• Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates -
  Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3x106 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials.
  🖺 Full Text HTML: Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates
• High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape -
  Understanding the mechanisms of immune evasion is critical for formulating an effective response to global threats like SARS-CoV2. We have fully decoded the immune synapses for multiple TCRs from acute patients, including cognate peptides and the presenting HLA alleles. Furthermore, using a newly developed mammalian epitope display platform (MEDi), we determined that several mutations present in multiple viral isolates currently expanding across the globe, resulted in reduced presentation by multiple HLA class II alleles, while some increased presentation, suggesting immune evasion based on shifting MHC-II peptide presentation landscapes. In support, we found that one of the mutations present in B1.1.7 viral strain could cause escape from CD4 T cell recognition in this way. Given the importance of understanding such mechanisms more broadly, we used MEDi to generate a comprehensive analysis of the presentability of all SARS-CoV-2 peptides in the context of multiple common HLA class II molecules. Unlike other strategies, our approach is sensitive and scalable, providing an unbiased and affordable high-resolution map of peptide presentation capacity for any MHC-II allele. Such information is essential to provide insight into T cell immunity across distinct HLA haplotypes across geographic and ethnic populations. This knowledge is critical for the development of effective T cell therapeutics not just against COVID-19, but any disease.
  🖺 Full Text HTML: High resolution profiling of MHC-II peptide presentation capacity, by Mammalian Epitope Display, reveals SARS-CoV-2 targets for CD4 T cells and mechanisms of immune-escape
• Perturbation of ACE2 structural ensembles by SARS-CoV-2 spike protein binding -
  The human ACE2 enzyme serves as a critical first recognition point of coronaviruses, including SARS-CoV-2. In particular, the extracellular domain of ACE2 interacts directly with the S1 tailspike protein of the SARS-CoV-2 virion through a broad protein-protein interface. Although this interaction has been characterized by X-ray crystallography and Cryo-EM, these structures do not reveal significant differences in ACE2 structure upon S1 protein binding. In this work, using several all-atom molecular dynamics simulations, we show persistent differences in ACE2 structure upon binding. These differences are determined with the Linear Discriminant Analysis (LDA) machine learning method and validated using independent training and testing datasets, including long trajectories generated by D. E. Shaw Research on the Anton 2 supercomputer. In addition, long trajectories for 78 potent ACE2-binding compounds, also generated by D. E. Shaw Research, were projected onto the LDA classification vector in order to determine whether the ligand-bound ACE2 structures were compatible with S1 protein binding. This allows us to predict which compounds are “apo-like” vs “complex-like”, as well as to pinpoint long-range ligand-induced allosteric changes of ACE2 structure.
  🖺 Full Text HTML: Perturbation of ACE2 structural ensembles by SARS-CoV-2 spike protein binding

From Clinical Trials

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

• Clinical Study in the Treatment of Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Molixan;   Drug: Placebo
  Sponsor:   Pharma VAM
  Not yet recruiting

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

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

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

• (CBDRA60) to Prevent or Reduce Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Dietary Supplement: CBDRA60 supplement;   Dietary Supplement: Placebo
  Sponsors:   Anewsha Therapeutics Inc.;   University of Michigan;   Biologics Consulting
  Not yet recruiting

• A Study to Evaluate UB-612 COVID-19 Vaccine in Adolescent, Younger and Elderly Adult Volunteers - Condition:   COVID-19
  Interventions:   Biological: UB-612;   Biological: Placebo
  Sponsors:   United Biomedical Inc., Asia;   COVAXX
  Recruiting

• Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ATR-002;   Drug: Placebo
  Sponsor:   Atriva Therapeutics GmbH
  Not yet recruiting

• JS016 (Anti-SARS-CoV-2 Monoclonal Antibody)With Mild and Moderate COVID-19 or SARS-CoV-2 Asymptomatic Infection Subects - Condition:   COVID-19
  Interventions:   Biological: Recombinant Human Anti-SARS-CoV-2 Monoclonal Antibody(25mg/kg;50mg/kg;100mg/kg);   Drug: Placebo
  Sponsor:   Shanghai Junshi Bioscience Co., Ltd.
  Recruiting

• Study of the Tolerability, Safety, Immunogenicity and Preventive Efficacy of the EpiVacCorona Vaccine for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: EpiVacCorona (EpiVacCorona vaccine based on peptide antigens for the prevention of COVID-19);   Other: Placebo (sodium chloride, a 0.9% solution for the preparation of dosage forms for injections)
  Sponsor:   Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”
  Active, not recruiting

• COVID-19 Treatment Cascade Optimization Study - Condition:   COVID-19 Testing
  Interventions:   Behavioral: Navigation Services;   Behavioral: Critical Dialogue;   Behavioral: Brief Counseling;   Behavioral: Referral and Digital Brochure
  Sponsors:   University of Illinois at Urbana-Champaign;   North Jersey Community Research Initiative;   National Institute on Minority Health and Health Disparities (NIMHD);   University of Michigan
  Recruiting

• Adoptive SARS-CoV-2 Specific T Cell Transfer in Patients at Risk for Severe COVID-19 - Condition:   Moderate COVID-19-infection
  Interventions:   Drug: IMP 1,000 plus SoC;   Drug: IMP 5,000 plus SoC;   Drug: IMP RP2D plus SoC;   Drug: SoC
  Sponsors:   Universitätsklinikum Köln;   ZKS Köln;   MMH Institute for Transfusion Medicine;   Miltenyi Biomedicine GmbH
  Not yet recruiting

• A Safety and Immunogenicity Study of Inactivated SARS-CoV-2 Vaccine (Vero Cells) in Healthy Population Aged 18 Years and Above(COVID-19) - Condition:   COVID-19
  Interventions:   Biological: medium dosage inactivated SARS-CoV-2 vaccine;   Biological: high dosage inactivated SARS-CoV-2 vaccine;   Biological: Placebo
  Sponsors:   Beijing Minhai Biotechnology Co., Ltd;   Shenzhen Kangtai Biological Products Co., LTD;   Jiangsu Province Centers for Disease Control and Prevention
  Active, not recruiting

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

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

From PubMed

• Targeting the Main Protease of SARS-CoV-2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors - The main protease of SARS-CoV-2 (Mpro), the causative agent of COVID-19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed Mpro. Two classes of protease inhibitors, azanitriles and pyridyl esters, were identified, optimized and subjected to in-depth biochemical characterization. Tailored peptides equipped with the…

• Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition - The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication….

• The type 2 asthma mediator IL-13 inhibits SARS-CoV-2 infection of bronchial epithelium - CONCLUSIONS: IL-13 markedly reduces susceptibility of HBECs to SARS-CoV-2 infection through mechanisms that likely differ from those activated by type I interferons. Our findings may help explain reports of relatively low prevalence of asthma in patients diagnosed with COVID-19 and could lead to new strategies for reducing SARS-CoV-2 infection.

• The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation - Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It…

• Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study - BACKGROUND: Patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus. Interleukin (IL)-1 or IL-6 inhibitors have been used to treat this patient population, but the comparative effectiveness of these different strategies remains undetermined. We aimed to compare IL-1 and IL-6 inhibition in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation.

• Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19 - Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against…

• Exploring existing drugs: proposing potential compounds in the treatment of COVID-19 - The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30^(th) of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7^(th) of February, 2021, though the actual figures may be much higher. Conserved…

• In-silico nucleotide and protein analyses of S-gene region in selected zoonotic coronaviruses reveal conserved domains and evolutionary emergence with trajectory course of viral entry from SARS-CoV-2 genomic data - CONCLUSION: phylogeny of SARS-CoV-2 genomic data suggests profiling in diverse populations with and without the outbreak alongside migration history and racial background for mutation tracking and dating of viral subtype divergence which is essential for effective management of present and future zoonotic coronavirus outbreaks.

• Needleless electrospun phytochemicals encapsulated nanofibre based 3-ply biodegradable mask for combating COVID-19 pandemic - The emergence of COVID-19 pandemic has severely affected human health and world economies. According to WHO guidelines, continuous use of face mask is mandatory for personal protection for restricting the spread of bacteria and virus. Here, we report a 3-ply cotton-PLA-cotton layered biodegradable face-mask containing encapsulated phytochemicals in the inner-filtration layer. The nano-fibrous PLA filtration layer was fabricated using needleless electrospinning of PLA & phytochemical-based…

• Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2: Antiviral Screening and Molecular Docking Studies - The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus. SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (2³) factorial design. In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors. Particle size (nm, Y1) and zeta…

• SARS-CoV-2 Nonstructural Proteins 1 and 13 Suppress Caspase-1 and the NLRP3 Inflammasome Activation - Viral infection-induced activation of inflammasome complexes has both positive and negative effects on the host. Proper activation of inflammasome complexes induces down-stream effector mechanisms that inhibit viral replication and promote viral clearance, whereas dysregulated activation has detrimental effects on the host. Coronaviruses, including SARS-CoV and MERS-CoV, encode viroporins that activate the NLRP3 inflammasome, and the severity of coronavirus disease is associated with the…

• Propolis in Metabolic Syndrome and Its Associated Chronic Diseases: A Narrative Review - Propolis is a resinous product collected by bees from plants to protect and maintain the homeostasis of their hives. Propolis has been used therapeutically by humans for centuries. This review article attempts to analyze the potential use of propolis in metabolic syndrome (MetS) and its associated chronic diseases. MetS and its chronic diseases were shown to be involved in at least seven out of the top 10 causes of death in 2019. Patients with MetS are also at a heightened risk of severe…

• Cell-free DNA maps COVID-19 tissue injury and risk of death, and can cause tissue injury - INTRODUCTION: Coronavirus 2019 (COVID-19) clinical course is heterogeneous, ranging from mild to severe multi-organ failure and death. In this study, we analyzed cell-free DNA (cfDNA) as a biomarker of injury to define the sources of tissue injury that contribute to such different trajectories.

• Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides - SARS-CoV-2 Spike protein RBD interacts with the hACE2 receptor to initiate cell entry and infection. We set out to develop lactam-based i,i + 4 stapled hACE2 peptides targeting SARS-CoV-2. In vitro screening demonstrates the inhibition of the Spike protein RBD-hACE2 complex formation by the hACE221-55A36K-F40E stapled peptide (IC50: 3.6 μM, Kd: 2.1 μM), suggesting that hACE2 peptidomimetics could form the basis for the development of anti-COVID-19 therapeutics.

• A comprehensive review of hydroxyurea for beta-haemoglobinopathies: the role revisited during COVID-19 pandemic - CONCLUSION: Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with β-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent β-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the…

From Patent Search

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

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

• 一种3-羟基丁酰化修饰蛋白质药物及其制备方法和应用 - 本发明涉及医药技术领域，公开了一种3‑羟基丁酰化修饰蛋白质药物（例如抗体）及其制备方法和应用，特别是一种3‑羟基丁酰化修饰抗体及其制备方法和应用。发明人经过大量实验发现，3‑羟基丁酸及其类似物修饰蛋白质药物（例如抗体）后，可以显著提高蛋白质药物的热稳定性、对蛋白酶水解的抗性，降低蛋白质药物的等电点，并显著延长其在受试者体内的半衰期，进而提高其药效。修饰后所得蛋白质药物在科研和临床方面具有广阔的应用前景和较高的商业价值。 - link

• 新冠病毒重组融合蛋白、其制备方法和应用 - 本发明提供一种新冠病毒重组融合蛋白、其制备方法和应用。本发明通过对新冠病毒S和N重组融合蛋白的基因序列进行设计，选择最优的片段进行整合，再通过人源HEK293细胞系统重组表达融合蛋白，经过纯化后对融合蛋白的分子量、纯度进行检测，最后利用融合蛋白制成新冠病毒抗体胶体金检测试纸条/试剂盒。与单独使用S蛋白或N蛋白制备的胶体金检测试纸条相比，该重组融合蛋白制备的胶体金检测试纸条具有更高的灵敏度和更低的漏检率。此外，本发明提供的新冠病毒重组融合蛋白可广泛应用于不同平台技术的新冠抗体检测试剂盒开发，如胶体金、荧光免疫层析、化学发光和酶联免疫等。 - link

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

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

• 一种新冠病毒S1蛋白的灌流生产系统及方法 - 本发明涉及细胞生物学技术领域，提供了一种新冠病毒S1蛋白的灌流生产系统及方法，包括：细胞反应器，用于培养表达S1蛋白的细胞株；灌流系统，包括过滤装置、出液管、回液管和第一循环泵，所述过滤装置的主体内设有孔径为0.1‑0.2μm的中空纤维柱，用于过滤透出液，截留细胞培养液中的S1蛋白；所述出液管的两端分别与所述细胞反应器和所述中空纤维柱的下端相连通；所述回液管的两端分别与所述细胞反应器和所述中空纤维柱的上端相连通；所述第一循环泵设置于所述出液管与所述中空纤维柱相连的管路中。本发明系统投入成本低且S1蛋白产量高。 - link

• 检测新冠病毒的方法及试剂盒 - 本发明公开了一种检测新冠病毒的方法及试剂盒。其中，该方法包括以下步骤：1）采集样本；2）采用核酸释放剂提取核酸；3）采用LAMP扩增进行检测，其中，核酸释放剂包括：热敏蛋白酶1000U/L~10000U/L、Tris‑HCl 5~50 mmol/L、曲拉通X‑100体积百分比0.05%_{0.5%和金属离子螯合剂0.1}0.5mmol/L，其余为无菌水，热敏蛋白酶为≥55℃加热5~10分钟会完全失活的蛋白酶。应用本发明的检测新冠病毒的方法及试剂盒，检测新冠病毒，检测周期短，操作简单方便，检测结果通俗易懂，检测特异性高，检测成本低。 - link

• 一种新型冠状病毒拉曼光谱数据中心的构建方法 - 本发明公开了一种新型冠状病毒拉曼光谱数据中心的构建方法，该方法包括以下步骤：S1.构建新冠病毒结构蛋白拉曼光谱数据库；S2.构建新冠病毒核酸拉曼光谱数据库；S3.构建新冠病毒颗粒拉曼光谱数据库；S4.构建新冠病毒临床检测样本拉曼光谱数据库；将各新型冠状病毒拉曼光谱数据库存入新型冠状病毒拉曼光谱检测服务器构成新型冠状病毒拉曼光谱数据中心。本发明有效建立了一套完整的新型冠状病毒拉曼光谱数据库，为新冠病毒拉曼检测技术提供可靠的标准数据支撑，有效提高检测结果的准确性及置信度。 - link