Covid-19 Sentry

Contents

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

From Preprints

• Evaluating Vaccine Efficacy Against SARS-CoV-2 Infection -

  Although interim results from several large placebo-controlled phase 3 trials demonstrated high vaccine efficacy (VE) against symptomatic COVID-19, it is unknown how effective the vaccines are in preventing people from becoming asymptomatically infected and potentially spreading the virus unwittingly. It is more difficult to evaluate VE against SARS-CoV-2 infection than against symptomatic COVID-19 because infection is not observed directly but rather is known to occur between two antibody or RT-PCR tests. Additional challenges arise as community transmission changes over time and as participants are vaccinated on different dates because of staggered enrollment or crossover before the end of the study. Here, we provide valid and efficient statistical methods for estimating potentially waning VE against SARS-CoV-2 infection with blood or nasal samples under time-varying community transmission, staggered enrollment, and blinded or unblinded crossover. We demonstrate the usefulness of the proposed methods through numerical studies mimicking the BNT162b2 phase 3 trial and the Prevent COVID U study. In addition, we assess how crossover and the frequency of diagnostic tests affect the precision of VE estimates.

  🖺 Full Text HTML: Evaluating Vaccine Efficacy Against SARS-CoV-2 Infection
• Using rapid (point-of-care) tests for COVID-19: A decision analysis comparing the expected benefit of two screening strategies -

  Background : Rapid tests for COVID-19 could be used to augment the otherwise limited laboratory-based testing capacity, but there are concerns that their utility may be compromised by their limited accuracy. The objective of this article is to compare the expected benefit (EB) of two screening strategies, one with rapid tests (SwRT) and another one without rapid tests (Sw ̅RT). Methods : We performed a decision analysis, with the overall EB defined as the proportion of correctly identified individuals minus the proportion of incorrectly identified individuals. Accordingly, the SwRT strategy will be deemed a better screening strategy if its lesser EB for COVID-19 free individuals is more than compensated by its greater EB for COVID-19 individuals. Otherwise, it will not. Results : As expected, the EB for COVID-19 individuals was greater for the SwRT strategy, with a far superior ability to rule out the presence of COVID-19. In fact, under the scenario of interest (i.e., 8000 ID Now rapid tests in addition to 28185 lab-based RT-PCR tests), it identified almost 16% more COVID-19 individuals than the Sw ̅RT strategy. In addition, the EB for COVID-19 free individuals was the same for both strategies, with a perfect ability at ruling in the presence of COVID-19. Conclusion : The SwRT strategy identified more COVID-19 individuals and this gain was not obtained at the detriment of COVID-19 free individuals who were equally well identified by both strategies. Hence, the SwRT strategy is a better screening strategy for COVID-19. It represents an opportunity to curtail the spread of SARS-CoV-2 that we may not afford to miss with new more contagious variants becoming more and more common in Canada.

  🖺 Full Text HTML: Using rapid (point-of-care) tests for COVID-19: A decision analysis comparing the expected benefit of two screening strategies
• Declines in life expectancy following the COVID-19 pandemic in provinces of Spain -

  The COVID-19 pandemic has impacted population health on a global scale. Most of the studies on mortality impacts are at national level, while broad evidence exists on heterogeneous COVID-19 incidence across regions and within countries. Using Spanish data for 2020, we estimate life expectancy changes in 2020 compared with the 2017-19 period in 50 Spanish provinces. We visualize longer-term trends (1990-2020), and compare the robustness of our province-specific results with cumulative COVID-19 incidence using regional data from the Spanish ENECOVID seroprevalence study. In 2020 there was a 1.2 and 1.1 year drop in life expectancy for men and women in Spain, but this impact was heterogeneous across regions. For men these losses were highest in the province of Segovia (-3.5 years decline), while for women the highest drop was observed in Salamanca (-2.8 years decline). Life expectancy actually increased in Santa Cruz de Tenerife (+1.1 and +0.6 years for men and women, respectively). Declines in life expectancy in 2020 were also highly correlated with the cumulative seroprevalence through November 2020 (ρ=0.80 and 0.77 in men and women, respectively). Monitoring regional life expectancy dynamics provide valuable and granular information on the heterogeneous impacts of the pandemic on health at the population level. Similar exercises in other European countries may reveal insightful geographic patterns in mortality impacts in COVID-19 pandemic years.

  🖺 Full Text HTML: Declines in life expectancy following the COVID-19 pandemic in provinces of Spain
• Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study -

  As large-scale immunization programs against COVID-19 proceed around the world, safety signals will emerge that need rapid evaluation.1,2 We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction, anaphylaxis, appendicitis, Bell s palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain-Barre syndrome, hemorrhagic and non-hemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, and transverse myelitis.3 We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.4 We analyzed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction, Guillain-Barre syndrome) increased with age, while others (e.g., anaphylaxis, appendicitis) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged ≥85 years. We report robust baseline rates of prioritized AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 vaccines.

  🖺 Full Text HTML: Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study
• Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals -

  The use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.

  🖺 Full Text HTML: Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals
• The influence of COVID-19-specific health risk beliefs on the motivation to quit smoking -
  In response to the COVID-19 pandemic, some smokers have experienced increased motivation to quit smoking, due to the higher risk of severe COVID-19 infection. However, this is not found across all smokers, and the motivation to quit appears dependent upon factors such as fear of COVID-19 and perceived risk from COVID-19. In the current investigation, specific COVID-19 risk beliefs were measured to isolate which beliefs predicted the motivation to quit smoking, these being the perceived severity of COVID-19 and perceived probability of COVID-19 infection. UK based smokers (N = 243) completed an online survey between September and October 2020, in which they reported their current motivation to quit smoking, fear of COVID-19, and their beliefs about how severe COVID-19 infection would be and how probable COVID-19 infection was. The only significant predictor of the motivation to quit smoking was the perceived probability of COVID-19 infection. This positive relationship remained when controlling for the general perceived probability and severity of other smoking related health conditions, suggesting a COVID-19-specific effect. Further, fear of COVID-19 only indirectly related to an increase in motivation to quit, when mediated through perceived probability of COVID-19 infection. The result places the perceived probability of COVID-19 infection as a central predictor of motivation to quit during the pandemic. Based on this evidence, messaging to smokers aiming to facilitate smoking cessation during the pandemic should focus on the highly contagious nature of the virus, to increase the motivation to quit.
  🖺 Full Text HTML: The influence of COVID-19-specific health risk beliefs on the motivation to quit smoking
• SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection -

  Background. Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods. A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results. Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or >8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions. Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

  🖺 Full Text HTML: SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection
• Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2. -

  The Oxford-Astra Zeneca COVID 19 vaccine (AZD1222 or ChAdOx1) is locally manufactured as Covishield by Serum Institute, Pune, India. In a group of 307 healthcare workers administered Covishield, we report measured antibody response to SARS-CoV-2 directed against the spike protein (S-antigen) at days 0, 7, 14, 28 and 45, with second dose on day 28 for all except 20 subjects who did not receive a second dose. In 129 subjects (42%) who had already developed antibodies to SARS-CoV-2 at day 0 (before immunization), it was observed that antibody response was significantly higher at each time point, with the maximum increase seen between days 0 and 7. The antibody levels and neutralizing activity in these subjects had peaked by day 28 and the second dose did not lead to further increase. Data from 9 subjects who were seropositive at baseline and received only one dose was similar to those who received both doses. In contrast the baseline sero-negative group (n=178) started developing antibody response only after 14 days or later. Administration of the second dose was associated with further increase in antibody levels at day 45 compared to day 28, with marked increase in neutralizing activity. In baseline seronegative subjects, who did not take the vaccine at day 28 (n=11), the antibody levels increased by about 2.5 folds between days 28 and 45, with minimal change in the neutralizing antibodies. In general, vaccination was well tolerated, and there were no group specific differences in post-vaccination symptomatology. Our data suggests that ChAdOx1 is highly immunogenic, particularly so where previous SARS CoV2 antibody-response is established. In such subjects, a single dose may be sufficient but in absence of such determination, both doses are required.

  🖺 Full Text HTML: Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2.
• The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout -

  The promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccine efficacy, vaccination rollout speeds, prioritization strategies, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy) selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence.

  🖺 Full Text HTML: The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout
• Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446 - S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, F61 and H121 exhibited efficient neutralizing activity against variants B.1.1.7 and B.1.351, those showed immune escape. Efficient neutralization of F61 and H121 against multiple mutations within RBD revealed a broad neutralizing activity against SARS-CoV-2 variants, which mitigated the risk of viral escape. Our findings defined the basis of therapeutic cocktails of F61 and H121 with broad neutralization and delivered a guideline for the current and future vaccine design, therapeutic antibody development, and antigen diagnosis of SARS-CoV-2 and its novel variants.
  🖺 Full Text HTML: Antibody Cocktail Exhibits Broad Neutralization against SARS-CoV-2 and SARS-CoV-2 variants
• Immunodominant B cell epitope in SARS-CoV-2 RBD comprises a B.1.351 and P.1 mutation hotspot: implications for viral spread and antibody escape -

  Recent SARS-CoV-2 variants pose important concerns due to their higher transmissibility (1) and escape (2) from previous infections or vaccine-induced neutralizing antibodies (nAb). The receptor binding domain (RBD) of the Spike protein is a major nAb target (3), but data on its B cell epitopes are still lacking. Using a peptide microarray, we identified an immunodominant epitope (S415-429) recognized by 68% of sera from 71 convalescent Brazilians infected with the ancestral variant. In contrast with previous studies, we have identified a linear IgG and IgA antibody binding epitope within the RBD. IgG and IgA antibody levels for this epitope positively correlated with nAb titers, suggesting a potential target of antibody neutralizing activity. Interestingly, this immunodominant RBD region harbors the mutation hotspot site K417 present in P.1 (K417T) and B.1.351 (K417N) variants. In silico simulation analyses indicate impaired RBD binding to nAb in both variants and that glycosylation in the B.1.351 417N could further hinder antibody binding as compared to the K417T mutation in P.1. This is in line with published data showing that nAb from either convalescents or anti-CoV-2 vaccinees are less effective towards B.1.351 than for P.1. Our data support the occurrence of immune pressure and selection involving this immunodominant epitope that may have critically contributed to the recent COVID-19 marked rise in Brazil and South Africa, and pinpoint a potential additional immune escape mechanism for SARS-CoV-2.

  🖺 Full Text HTML: Immunodominant B cell epitope in SARS-CoV-2 RBD comprises a B.1.351 and P.1 mutation hotspot: implications for viral spread and antibody escape
• A Randomized Trial of Otilimab in Severe COVID-19 Pneumonia (OSCAR) -

  BACKGROUND Increasing age is a risk factor for COVID-19 severity and mortality; emerging science implicates GM-CSF and dysregulated myeloid cell responses in the pathophysiology of severe COVID-19. METHODS We conducted a large, global, double-blind, randomized, placebo-controlled study evaluating a single 90 mg infusion of otilimab (human anti-GM-CSF monoclonal) plus standard of care in adults hospitalized with severe COVID-19 respiratory failure and systemic inflammation, stratified by age and clinical status. Primary outcome was the proportion of patients alive and free of respiratory failure at Day 28; secondary endpoints included all-cause mortality at Day 60. RESULTS Overall, 806 patients were randomized (1:1); 71% of patients receiving otilimab were alive and free of respiratory failure at Day 28 versus 67% receiving placebo, although this did not reach statistical significance (model-adjusted difference 5.3% [95% CI 0.8, 11.4]; p=0.09). However, there was a benefit in the pre-defined ≥70-year age group (model-adjusted difference 19.1% [95% CI 5.2, 33.1]; nominal p=0.009); these patients also had a reduction of 14.4% (95% CI 0.9, 27.9%; nominal p=0.04) in model-adjusted all-cause mortality at Day 60. Safety findings were comparable between otilimab and placebo, and consistent with severe COVID-19. CONCLUSIONS Although not statistically significant in the overall population, otilimab demonstrated a substantial benefit in patients aged ≥70, possibly reflecting a population that could benefit from therapeutic blocking of GM-CSF in severe COVID-19 where myeloid cell dysregulation is predominant. These findings are being confirmed in a further cohort of patients aged ≥70 in Part 2 of this study. (ClinicalTrials.gov number: NCT04376684).

  🖺 Full Text HTML: A Randomized Trial of Otilimab in Severe COVID-19 Pneumonia (OSCAR)
• The effect of antibody test result knowledge on transmission reducing behaviours -
  This study explored the effect knowledge of antibody status has on compliance with transmission reducing behaviours (TRBs). Participants (n=82) comprised of NHS Lothian staff and individuals enrolled in the BioResource study with community diagnosed and treated SARS-CoV-2 infections. They completed a baseline health beliefs questionnaire, provided blood samples for antibody testing and received result 2-4 weeks later. Around 2-4 weeks later, participants completed follow-up health belief questionnaires. The questionnaire was designed based on the constructs of the Health Belief Model, the most prominent framework for understanding why individuals may or may not act in the face of a threat. Fifty-six participants completed the follow-up health belief questionnaires. Knowledge of antibody status did not affect compliance with TRBs. Increased perceived benefits, cues to action and self-efficacy, and decreased perceived barriers, to comply with TRBs was significantly associated with higher compliance. No significant correlation was found between measures of susceptibility or severity and compliance with TRBs. Interventions to increase perceived benefits, cues to action and self-efficacy, and decrease barriers, to engaging in TRBs should be explored.
  🖺 Full Text HTML: The effect of antibody test result knowledge on transmission reducing behaviours
• Effects of scientific literacy on attitudes toward COVID-19 vaccinations and preventive behaviors: A pre-registered study -
  The ongoing COVID-19 pandemic, which began in early 2020, is a global public health crisis. To prevent the spread of COVID-19, it is necessary to promote vaccine administration and preventive behaviors (e.g., mask, handwashing, social distancing). However, some people have negative attitudes toward vaccine administration and preventive behaviors. The present study investigated how scientific literacy and perceived understanding of COVID-19 influence attitudes toward COVID-19 vaccinations and preventive behaviors. The findings demonstrated that both scientific literacy and perceived understanding of COVID-19 vaccines were positively associated with attitudes toward COVID-19 vaccines. Additionally, perceived understanding of COVID-19 preventive behaviors (but not scientific literacy) was positively associated with attitudes toward/practice of COVID-19 preventive behaviors. Collectively, our findings revealed the role of cognitive factors in preventing the global public health crisis and demonstrated the effects of objective and subjective knowledge on attitudes toward COVID-19 vaccinations and preventive behaviors.
  🖺 Full Text HTML: Effects of scientific literacy on attitudes toward COVID-19 vaccinations and preventive behaviors: A pre-registered study
• Using Absolutist Word Frequency from Online Searches to Measure Population Mental Health Dynamics -
  The assessment of population mental health relies on survey data from representative samples, which come with considerable costs. Drawing on research which established that absolutist words (e.g. never) are semantic markers for depression, we propose a new measure of population mental health based on the frequency of absolutist words in online search data (Absolute Thinking Index; ATI). Our aims were to first validate the ATI, and to use it to model public mental health dynamics in France and the UK during the current COVID-19 pandemic. To do so, we extracted time series for a validated dictionary of 19 absolutist words, from which the ATI was computed (weekly averages, 2019-2020, n = 208). We then tested the relationship between ATI and longitudinal survey data of population mental health in the UK and France. ATI was linked with survey depression scores in the UK, r = .68, 95%CI[.34,.86], β = .23, 95%CI[.09,.37] in France and displayed similar trends. We finally assessed the pandemic’s impact on ATI using Bayesian structural time-series models. These revealed that the pandemic increased ATI by 3.2%, 95%CI[2.1,4.2] in France and 3.7%, 95%CI[2.9,4.4] in the UK. Mixed-effects models showed that ATI was related to COVID-19 new deaths in both countries β = .14, 95%CI[.14,.21]. Our results demonstrate the validity of the ATI as a measure of population mental health (depression) in France and the UK. We propose that researchers use it as cost-effective public mental health “thermometer” for applied and research purposes.
  🖺 Full Text HTML: Using Absolutist Word Frequency from Online Searches to Measure Population Mental Health Dynamics

From Clinical Trials

• Clinical Study in the Treatment of Patients With Moderate Course of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: COVID-globulin;   Drug: Placebo
  Sponsor:   Microgen
  Not yet recruiting

• Rehabilitation for Patients With Persistent Symptoms Post COVID-19 - Condition:   Covid19
  Intervention:   Other: Concentrated rehabilitation for patients with persistent symptoms post COVID-19
  Sponsors:   Western Norway University of Applied Sciences;   Helse-Bergen HF
  Recruiting

• A Nurse-Community Health Worker-Family Partnership Model: Addressing Uptake of COVID-19 Testing and Control Measures - Condition:   COVID-19
  Intervention:   Behavioral: Nurse-Community-Family Partnership Intervention
  Sponsor:   New York University
  Not yet recruiting

• Efficacy and Safety of Three Different Doses of an Anti SARS-CoV-2 Hyperimmune Equine Serum in COVID-19 Patients - Condition:   Covid19
  Interventions:   Biological: Anti SARS-CoV-2 equine hyperimmune serum;   Biological: placebo
  Sponsors:   Caja Costarricense de Seguro Social;   Universidad de Costa Rica;   Ministry of Health Costa Rica
  Not yet recruiting

• Viral Clearance, PK and Tolerability of Ensovibep in COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: ensovibep
  Sponsor:   Molecular Partners AG
  Recruiting

• A Clinical Study Evaluating Inhaled Aviptadil on COVID-19 - Condition:   Covid19
  Interventions:   Drug: Inhaled Aviptadil;   Drug: Placebo
  Sponsors:   Centurion Pharma;   Klinar CRO
  Recruiting

• The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome - Condition:   COVID-19
  Intervention:   Other: Exercise
  Sponsor:   Medical University of Vienna
  Recruiting

• ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 - Condition:   Covid19
  Interventions:   Biological: Remdesivir;   Drug: Remdesivir placebo;   Biological: VIP;   Drug: VIP Placebo;   Drug: Corticosteroid
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   NeuroRx, Inc.
  Not yet recruiting

• Safety and Immunogenicity of the Inactivated Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine Compared to Placebo - Condition:   COVID-19 Vaccine
  Interventions:   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 4 µg/0.5 ml Vaccine;   Biological: Koçak-19 Inaktif Adjuvanlı COVID-19 Vaccine 6 µg/0.5 ml Vaccine;   Biological: Placebo
  Sponsor:   Kocak Farma
  Recruiting

• Study on Sequential Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine - Condition:   COVID-19
  Interventions:   Biological: recombinant Ad5 vectored COVID-19 vaccine;   Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19;   Biological: trivalent split influenza vaccine
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Recruiting

• Total-Body Parametric 18F-FDG PET of COVID-19 - Condition:   Covid19
  Intervention:   Device: uEXPLORER/mCT
  Sponsor:   University of California, Davis
  Recruiting

• Omega-3 Oil Use in COVID-19 Patients in Qatar - Condition:   COVID-19
  Intervention:   Drug: Omega 3 fatty acid
  Sponsor:   Hamad Medical Corporation
  Recruiting

• Cetirizine and Famotidine for COVID-19 - Condition:   Covid19
  Interventions:   Drug: Cetirizine and Famotidine;   Drug: Placebo
  Sponsor:   Emory University
  Not yet recruiting

• TCB008 in Patients With COVID-19 - Condition:   Covid19
  Intervention:   Drug: TCB008
  Sponsor:   TC Biopharm
  Not yet recruiting

• Evaluation of Anti-COVID 19 Pfizer Vaccination Effect on COVID 19 Detection Using Breath Analysis - Condition:   Covid19
  Intervention:   Diagnostic Test: vaccination against COVID19
  Sponsor:   Scentech Medical Technologies Ltd
  Recruiting

From PubMed

• High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors - A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main…

• Multi-conformation representation of Mpro identifies promising candidates for drug repurposing against COVID-19 - The COVID-19 main protease (Mpro), one of the conserved proteins of the novel coronavirus is crucial for its replication and so is a very lucrative drug target. Till now, there is no drug molecule that has been convincingly identified as the inhibitor of the function of this protein. The current pandemic situation demands a shortcut to quickly reach to a lead compound or a drug, which may not be the best but might serve as an interim solution at least. Following this notion, the present…

• Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model - The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered…

• Novel inhibitors of the main protease enzyme of SARS-CoV-2 identified via molecular dynamics simulation-guided in vitro assay - For the COVID-19 pandemic caused by SARS-CoV-2, there are currently no effective drugs or vaccines to treat this coronavirus infection. In this study, we focus on the main protease enzyme of SARS-CoV-2, 3CL^(pro), which is critical for viral replication. We employ explicit solvent molecular dynamics simulations of about 150 compounds docked into 3CL^(pro)’s binding site and that had emerged as good main protease ligands from our previous in silico screening of over 1.2 million compounds. By…

• Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone - An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 cytokine storm. In this study, the effects of a recombinant SARS-CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation of PBMCs with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNFα, IL-6, IL-1β and IL-8….

• Polysulfates block SARS-CoV-2 uptake via electrostatic interactions - Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC 50 ) of 67 μg/mL (approx. 1.6 μM). This synthetic polysulfate exhibits more than 60-fold higher…

• Wuhan to World: The COVID-19 Pandemic - COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family Coronaviridae. It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier…

• Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film…

• SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization - Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health and…

• Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir - The SARS-CoV-2 replication and transcription complex (RTC) comprising nonstructural protein (nsp) 2-16 plays crucial roles in viral replication, reducing the efficacy of broad-spectrum nucleoside analog drugs such as remdesivir and evading innate immune responses. Most studies target a specific viral component of the RTC such as the main protease or the RNA-dependent RNA polymerase. In contrast, our strategy is to target multiple conserved domains of the RTC to prevent SARS-CoV-2 genome…

• Intriguing Antiviral Modified Nucleosides: A Retrospective View into the Future Treatment of COVID-19 - Great pioneers of nucleic acid chemistry had elucidated nucleic acid functions and structures and developed various antiviral modified nucleoside drugs. It is possible in theory that antiviral modified nucleosides prevent viral replication by inhibiting viral polymerases. However, biological phenomena far exceed our predictions at times. We describe the characteristics of the approved antiviral modified nucleosides from an organic chemistry perspective. Also, based on our experiences and…

• Angiotensin Receptor Blockers for COVID-19: Pathophysiological and Pharmacological Considerations About Ongoing and Future Prospective Clinical Trials - COVID-19 pandemic demands a swift response to find therapeutic tools that effectively reduce morbidity and mortality. Despite initial fears, evidence from retrospective observational studies supports the inhibition of the renin-angiotensin system as an emerging pathway to delay or moderate angiotensin II-driven lung inflammation. This has triggered several prospective clinical trials. In this commentary we provide an overview and analysis of current ongoing clinical trials aimed at evaluating…

• Epstein-Barr virus lytic replication induces ACE2 expression and enhances SARS CoV-2 pseudotyped virus entry in epithelial cells - Understanding factors that affect the infectivity of SARS CoV-2 is central to combatting COVID-19. The virus surface spike protein of SARS CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We find that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using VSV particles pseudotyped with the SARS CoV-2 spike protein, we show that lytic EBV replication enhances…

• C5aR inhibition of non-immune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia - CONCLUSION: Crucially, we illustrate here for the first time, that targeting the anaphylotoxin receptors C3aR and C5aR in non-immune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.

• Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells - COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate that…

From Patent Search

• Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link

• 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

• AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - link

• 一种肝素类药物组合物、喷鼻剂及其制备方法及应用 - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用，普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组（p<0.05）。 - 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

• 抗SARS-COV-2中和抗体 - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - link

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

• Method and compositions for treating coronavirus infection - A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection. - link

• **一种4-肟-5-（2-甲基丙酰基）尿苷的制备方法** - 本发明公开了一种4‑肟‑5‑（2‑甲基丙酰基）尿苷的制备方法，包括：S1：在酸存在条件下，使得化合物1和2,2‑二甲氧基丙烷在有机溶剂中反应得到化合物2；S2：在碱存在条件下，使得化合物2在有机溶剂中反应得到化合物3；S3：在羟胺水溶液存在条件下使化合物3在有机溶剂中反应得到化合物4；S4：在酸存在条件下使化合物4在有机溶剂中反应得到化合物I。本发明制备得到的结晶性能良好的固体，且制备条件简单，转化率以及原子经济性好。 - link

• 一种COVID-19假病毒及其制备方法和用途 - 本发明涉及生物技术领域，特别是涉及一种COVID‑19假病毒及其制备方法和用途本发明，所述COVID‑19假病毒由外壳蛋白质粒与辅助质粒经病毒包装而成，所述外壳蛋白质粒包括表达COVID‑19 S蛋白的质粒、表达COVID‑19 M蛋白的质粒和表达COVID‑19 E蛋白的质粒。本发明的COVID‑19假病毒采用三质粒系统包装，以S/M/E蛋白替代表达VSV‑G蛋白，比仅含有S蛋白的假病毒感染能力更强、灵敏度更高。而且，COVID‑19假病毒携带两种荧光报告基团，不同的荧光报告基团可应用于不同的场景，使得COVID‑19假病毒应用时更简便。 - link