Covid-19 Sentry

Contents

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

From Preprints

• Containing the Spread of Infectious Disease on College Campuses -

  College campuses are highly vulnerable to infectious diseases outbreaks, and there is a mounting need to develop strategies that best mitigate their size and duration, particularly as colleges consider reopening their campuses in the midst of the COVID-19 pandemic. Towards addressing this need, we applied a stochastic transmission model to quantify the impact of university-level responses to past outbreaks on their campuses and used it to determine which control interventions are most effective. The model aims to simultaneously overcome three crucial issues: stochastic variation in small populations, missing or unobserved case data, and changes in disease transmission rates post-intervention. We tested the model and assessed various interventions using data from the 2014 and 2016 mumps outbreaks at Ohio State University and Harvard University, respectively. Our results suggest that universities should design more aggressive diagnostic procedures and stricter isolation policies to decrease infectious disease incidence on campus. Our model can be applied to data from other outbreaks in college campuses and similar small- population settings.

  🖺 Full Text HTML: Containing the Spread of Infectious Disease on College Campuses
• Propensity to reappraise promotes resilience to stress-induced negativity bias -
  Stress exposure is associated with an increased tendency to appraise ambiguous social stimuli as negative. However, it remains unknown whether tendencies to use emotion regulation strategies—such as cognitive reappraisal, which involves altering the meaning of affective stimuli—can buffer these stress effects on social evaluations. Here, we examined whether increased reappraisal use confers resilience against stress-induced negativity bias. In Study 1, healthy participants (n=43) rated the valence of emotionally ambiguous (surprised) faces before and after an acute stress or control manipulation and reported reappraisal habits. Increased negativity ratings were milder for stressed individuals that reported more habitual reappraisal use. In Study 2 (n=97), we extended this investigation to real-world perceived stress before and during the COVID-19 pandemic. We found that reappraisal tendency moderates the relationship between perceived stress and increased negativity bias. Collectively, these findings suggest that the propensity to reappraise attenuates stress-induced negativity bias when evaluating others under uncertainty.
  🖺 Full Text HTML: Propensity to reappraise promotes resilience to stress-induced negativity bias
• Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond? -
  Definitive antiviral properties are evidenced for niacin, i.e., nicotinic acid (NA), as coronavirus disease 2019 (COVID-19) therapy for both disease recovery and prevention, to the level that reversal or progression of its pathology follows as an intrinsic function of NA supply. This detailed investigation provides a thorough disentanglement of how the downstream inflammatory propagation of ensuing severe acute respiratory virus 2 (SARS-CoV-2) infection is entirely prohibited or reversed upstream out the body to expeditiously restore health with well-tolerated dynamic supplementation of sufficient NA (i.e., ~1-3 grams per day). Culmination of this research leads to realization of the potentially ubiquitous therapeutic and preventive powers of NA against inflammatory disease, in general.
  🖺 Full Text HTML: Sufficient niacin supply: the missing puzzle piece to COVID-19, and beyond?
• The COVID-19 Pandemic’s Impact on OCD Symptoms Varies Widely -
  We conducted a survey of adults with OCD during COVID-19, but found a much higher rate of OCD symptom worsening than similar studies did. Here, we describe our study and discuss potential reasons for these differing patterns of results.
  🖺 Full Text HTML: The COVID-19 Pandemic’s Impact on OCD Symptoms Varies Widely
• Losartan promotes cell survival following SARS-CoV-2 infection in vitro -
  Warning: This manuscript presents an in vitro study pending validation by clinical trials. Introduction: Coronavirus disease 2019 (COVID-19) can be associated with mortality and high morbidity worldwide. There is an extensive effort to control infection and disease caused by SARS-CoV-2. This study addressed the hypothesis that angiotensin II type I receptor blocker, Losartan, may restrict pathogenesis caused by SARS-CoV-2 by decreasing viral-induced cytopathological changes by blocking angiotensin II type 1 receptor (AT1R), thus reducing the affinity of the virus for ACE2, and inhibiting papain-like protease of the virus. Method: Losartan inhibitory effect on deubiquitination and deISGylation properties of papain-like protease was investigated using a fluorescence method and gel shift analysis determining its inhibitory effects. The inhibitory effect of Losartan on SARS-CoV-2 cell replication was investigated both when losartan was added to the cell culture 1 hour before (pre-infection group) and 1 hour after (post-infection group) SARS-CoV-2 infection of Vero E6 cells. Results: Losartan treatment of Vero E6 cells prior to and after SARS-CoV-2 infection reduced SARS-CoV-2 replication by 80% and 70% respectively. Losartan was not a strong deubiquitinase and deISGylase inhibitor of PLpro. Conclusion: Losartan added pre- and post-infection to the Vero E6 cell culture significantly prevents cell destruction and replication by SARS-CoV2. Losartan has low side-effects, is readily available, and can be produced at high levels globally, all features of a promising drug in treatment of COVID-19 if validated by clinical trials.
  🖺 Full Text HTML: Losartan promotes cell survival following SARS-CoV-2 infection in vitro
• SARS-CoV-2 disease severity and transmission efficiency is increased for airborne but not fomite exposure in Syrian hamsters -
  Transmission of SARS-CoV-2 is driven by contact, fomite, and airborne transmission. The relative contribution of different transmission routes remains subject to debate. Here, we show Syrian hamsters are susceptible to SARS-CoV-2 infection through intranasal, aerosol and fomite exposure. Different routes of exposure presented with distinct disease manifestations. Intranasal and aerosol inoculation caused more severe respiratory pathology, higher virus loads and increased weight loss. Fomite exposure led to milder disease manifestation characterized by an anti-inflammatory immune state and delayed shedding pattern. Whereas the overall magnitude of respiratory virus shedding was not linked to disease severity, the onset of shedding was. Early shedding was linked to an increase in disease severity. Airborne transmission was more efficient than fomite transmission and dependent on the direction of the airflow. Carefully characterized of SARS-CoV-2 transmission models will be crucial to assess potential changes in transmission and pathogenic potential in the light of the ongoing SARS-CoV-2 evolution.
  🖺 Full Text HTML: SARS-CoV-2 disease severity and transmission efficiency is increased for airborne but not fomite exposure in Syrian hamsters
• SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma -
  To investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.
  🖺 Full Text HTML: SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma
• Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic protection -
  SARS-CoV-2 has caused the global COVID-19 pandemic. Although passively delivered neutralizing antibodies against SARS-CoV-2 show promise in clinical trials, their mechanism of action in vivo is incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected animals. Whereas Fc effector functions are dispensable when representative neutralizing mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters better than loss-of-function Fc variant mAbs. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and preserved tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes for therapeutic efficacy. Thus, potently neutralizing mAbs require Fc effector functions for maximal therapeutic benefit during therapy to modulate protective immune responses and mitigate lung disease.
  🖺 Full Text HTML: Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic protection
• Emerging SARS-CoV-2 diversity revealed by rapid whole genome sequence typing. -
  Background: Discrete classification of SARS-CoV-2 viral genotypes can identify emerging strains and detect geographic spread, viral diversity, and transmission events. Methods: We developed a tool (GNUVID) that integrates whole genome multilocus sequence typing and a supervised machine learning random forest-based classifier. We used GNUVID to assign sequence type (ST) profiles to each of 69,686 SARS-CoV-2 complete, high-quality genomes available from GISAID as of October 20th 2020. STs were then clustered into clonal complexes (CCs), and then used to train a machine learning classifier. We used this tool to detect potential introduction and exportation events, and to estimate effective viral diversity across locations and over time in 16 US states. Results: GNUVID is a scalable tool for viral genotype classification (available at https://github.com/ahmedmagds/GNUVID) that can be used to quickly process tens of thousands of genomes. Our genotyping ST/CC analysis uncovered dynamic local changes in ST/CC prevalence and diversity with multiple replacement events in different states. We detected an average of 20.6 putative introductions and 7.5 exportations for each state. Effective viral diversity dropped in all states as shelter-in-place travel-restrictions went into effect and increased as restrictions were lifted. Interestingly, our analysis showed correlation between effective diversity and the date that state-wide mask mandates were imposed. Conclusions: Our classification tool uncovered multiple introduction and exportation events, as well as waves of expansion and replacement of SARS-CoV-2 genotypes in different states. Combined with future genomic sampling the GNUVID system could be used to track circulating viral diversity and identify emerging clones and hotspots.
  🖺 Full Text HTML: Emerging SARS-CoV-2 diversity revealed by rapid whole genome sequence typing.
• MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans -
  SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.
  🖺 Full Text HTML: MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans
• Prevalence of bacterial pathogens and potential role in COVID-19 severity in patients admitted to intensive care units in Brazil -

  Secondary bacterial and fungal infections are associated with respiratory viral infections and invasive mechanical ventilation. In Coronavirus disease 2019 (COVID-19), lung injury by SARS-CoV-2 and impaired immune response can provide a favorable environment for microorganism growth and colonization in hospitalized individuals. Recent studies suggest that secondary bacterial pneumonia is a risk factor associated with COVID-19. In Brazil, knowledge about microbiota present in COVID-19 patients is incipient. This work describes the microbiota of 21 COVID-19 patients admitted to intensive care units from two Brazilian centers. We identified respiratory, nosocomial and bacterial pathogens as prevalent microorganisms. Other bacterial opportunistic and commensal species are also represented. Virulence factors of these pathogenic species, metabolic pathways used to evade and modulate immunological processes and the interconnection between bacterial presence and virulence in COVID-19 progression are discussed.

  🖺 Full Text HTML: Prevalence of bacterial pathogens and potential role in COVID-19 severity in patients admitted to intensive care units in Brazil
• Exploring drugs and vaccines associated with altered risks and severity of COVID-19: a UK Biobank cohort study of all ATC level-4 drug categories -

  Background: COVID-19 is a major public health concern, yet its risk factors are not well-understood and effective therapies are lacking. It remains unclear how different drugs may increase or decrease the risks of infection and severity of disease. Methods: We studied associations of prior use of all level-4 ATC drug categories (including vaccines) with COVID-19 diagnosis and outcome, based on a prospective cohort of UK Biobank (UKBB). Drug history was based on general practitioner(GP) records. Effects of prescribed medications/vaccinations on the risk of infection, severity of disease and mortality were investigated separately. Hospitalized and fatal cases were categorized as severe infection. We also considered different study designs and conducted analyses within infected patients, tested subjects and the whole population respectively, and for 5 different time-windows of prescriptions. Missing data were accounted for by multiple imputation and inverse probability weighting was employed to reduce testing bias. Multivariable logistic regression was conducted which controls for main confounders. Results: We placed a greater focus on protective associations here, as (residual) confounding by indication and comorbidities tends to bias towards harmful effects. Across all categories, statins showed the strongest and most consistent protective associations. Significant protective effects against severe infection were seen among infected subjects (OR for prescriptions within a 12-month window, same below: 0.50, 95% CI:0.42-0.60), tested subjects (OR=0.63, 0.54-0.73) or in the general population (OR=0.49, 0.42-0.57). A number of top-listed drugs with protective effects were also cardiovascular medications, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blocker and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones and proton pump inhibitors, among others. Interestingly, we also observed protective associations by numerous vaccines. The most consistent association was observed for influenza vaccines, which showed reduced odds of infection (OR= 0.73 for vaccination in past year, CI 0.65-0.83) when compared cases to general population controls or test-negative controls (OR=0.60, 0.53-0.68). Protective associations were also observed when severe or fatal infection was considered as the outcome. Pneumococcal, tetanus, typhoid and combined bacterial and viral vaccines (ATC code J07CA) were also associated with lower odds of infection/severity. Further subgroup and interaction analyses revealed difference in protective effects in different clinical subgroups. For example, protective effects of flu and pneumococcal vaccines were weaker in obese individuals, while we observed stronger protective effects of statins in those with cardiometabolic disorders, such as diabetes, coronary artery disease, hypertension and obesity. Conclusions: A number of drugs, including many for cardiometabolic disorders, may be associated with lower odds of infection/severity of infection. Several existing vaccines, especially flu vaccines, may be beneficial against COVID-19 as well. However, causal relationship cannot be established due to risk of confounding. While further studies are required to validate the findings, this work provides a useful reference for future meta-analyses, clinical trials or experimental studies.

  🖺 Full Text HTML: Exploring drugs and vaccines associated with altered risks and severity of COVID-19: a UK Biobank cohort study of all ATC level-4 drug categories
• Are the SIR and SEIR models suitable to estimate the basic reproduction number for the CoViD-19 epidemic? -

  The transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes pandemic but presents different incidences in the world. Mathematical models were formulated to describe the coronavirus disease 2019 (CoViD-19) epidemic in each country or region. At the beginning of the pandemic, many authors used the SIR (susceptible, infectious, and recovered compartments) and SEIR (including exposed compartment) models to estimate the basic reproduction number R0 for the CoViD-19 epidemic. These simple deterministic models assumed that the only available collection of the severe CoViD-19 cases transmitted the SARS-CoV-2 and estimated lower values for R0, ranging from 1.5 to 3.0. However, the major flaw in the estimation of R0 provided by the SIR and SEIR models was that the severe CoViD-19 patients were hospitalized, and, consequently, not transmitting. Hence, we proposed a more elaborate model considering the natural history of CoViD-19: the inclusion of asymptomatic, pre-symptomatic, mild and severe CoViD-19 compartments. The model also encompassed the fatality rate depending on age. This SEAPMDR model estimated R0 using the severe CoViD-19 data from São Paulo State (Brazil) and Spain, yielding higher values for R0, that is, 6.54 and 5.88, respectively. It is worth stressing that this model assumed that severe CoViD-19 cases were not participating in the SARS-CoV-2 transmission chain. Therefore, the SIR and SEIR models are not suitable to estimate R0 at the beginning of the epidemic by considering the isolated severe CoViD-19 data as transmitters.

  🖺 Full Text HTML: Are the SIR and SEIR models suitable to estimate the basic reproduction number for the CoViD-19 epidemic?
• The effect of a national lockdown in response to COVID-19 pandemic on the prevalence of clinical symptoms in the population -

  The vast and rapid spread of COVID-19 calls for immediate action from policy-makers, and indeed various lockdown measures were implemented in many countries. Here, we utilized nationwide surveys that assess COVID-19 associated symptoms to analyze the effect of the lockdown policy in Israel on the prevalence of clinical symptoms in the population. Daily symptom surveys were distributed online and included fever, respiratory symptoms, gastrointestinal symptoms, anosmia and Ageusia. A total of 1,456,461 survey responses were analyzed. We defined a single measure of symptoms, Symptoms Average (SA), as the mean number of symptoms reported by responders. Data were collected between March 15th to May 11th, 2020. Notably, following severe lockdown measures, we found that between March 15th and April 20th, SA sharply declined by 83.8%, as did every individual symptom, including the most common symptoms reported by our responders, cough and rhinorrhea andnasal congestion, which decreased by 74.1% and 69.6%, respectively. Individual symptoms exhibit differences in reduction dynamics, suggesting differences in the medical conditions that they represent or in the nature of the symptoms themselves. The reduction in symptoms was observed in all the cities in Israel, and in several stratifications of demographic characteristics. Between April 20th and May 11th, following several subsequent lockdown relief measures, the decrease in SA and individual symptoms halted and they remain relatively stable with no significant change. Overall, these results demonstrate a profound decrease in a variety of clinical symptoms following the implementation of a lockdown in Israel. As our survey symptoms are not specific to COVID-19 infection, this effect likely represents an overall nationwide reduction in the prevalence of infectious diseases, including COVID-19. This quantification may be of major interest for COVID-19 pandemic, as many countries consider implementation of lockdown strategies.

  🖺 Full Text HTML: The effect of a national lockdown in response to COVID-19 pandemic on the prevalence of clinical symptoms in the population
• Modeling the flow of the COVID-19 in Germany: The efficacy of lockdowns and social behavior -

  This study develops a computer simulation in understanding the flow of the COVID-19 in Germany between January 2020 and July 2020. This aims to analyze not only the flow of the COVID-19 but also the efficacy of taken measures during the given period. The computer model is based on the SEIR concept and it is based on the system dynamics approach in which some uncertain parameters are estimated through the calibration process. Moreover, the SEIR computer model is developed by considering different flows of COVID-19 cases in older and young people in Germany. This study successfully reproduces similar patterns of infected, recovered, and death cases. Moreover, as the SEIR model can successfully reproduce similar patterns, the SEIR model can be a basis to estimate other resources such as health workers and bed capacities.

  🖺 Full Text HTML: Modeling the flow of the COVID-19 in Germany: The efficacy of lockdowns and social behavior

From Clinical Trials

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

• Dendritic Cell Vaccine to Prevent COVID-19 - Condition:   COVID-19
  Intervention:   Biological: AV-COVID-19
  Sponsors:   Indonesia-MoH;   Aivita Biomedical, Inc.;   PT AIVITA Biomedika Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   RSUP Dr. Kariadi Semarang, indonesia;   Faculty of Medicine University of Diponegoro, Indonesia
  Recruiting

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

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

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

• suPAR-Guided Anakinra Treatment for Management of Severe Respiratory Failure by COVID-19 - Condition:   Covid19
  Interventions:   Drug: Anakinra;   Drug: Placebo
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Recruiting

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

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

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

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

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

• Study in Adults to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, Given in Combination With rAd26-S, Recombinant Adenovirus Type 26 Component of Gam-COVID-Vac Vaccine, for the Prevention of COVID-19. - Condition:   COVID-19
  Interventions:   Biological: AZD1222;   Biological: rAd26-S
  Sponsors:   R-Pharm;   AstraZeneca
  Not yet recruiting

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

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

• Efficacy and Safety of hzVSF-v13 in Patients With COVID-19 Pneumonia - Condition:   COVID-19
  Interventions:   Drug: hzVSF-v13;   Drug: Placebo (Normal saline solution)
  Sponsor:   ImmuneMed, Inc.
  Recruiting

From PubMed

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread worldwide and has affected more than 10 million individuals. A typical feature of COVID-19 is the suppression of type I and III interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism by which SARS-CoV-2 evades antiviral immunity remains elusive. Here, we reported that the SARS-CoV-2 membrane (M) protein inhibits the production of type I and III...

• The potential mechanism of N-acetylcysteine in treating COVID-19 - N-Acetylcysteine (NAC) has been proposed and used to treat coronavirus disease 2019 (COVID-19). By reviewing the existing pathological studies of COVID-19, it was found that abundant mucus secretion, formation of a hyaline membrane (supportive of acute respiratory distress syndrome), and interstitial fibrous exudation may be important characteristics of COVID-19 and may be pathological targets of drug therapy. In addition, multiple extrapulmonary organ injuries in COVID-19 may be associated with...

• The fight against human viruses: how NMR can help - CONCLUSION: Considering the NMR-based work conducted on different viruses, we believe that in the close future much more NMR efforts will be devoted to discover novel anti SARS-CoV-2 agents.

• Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions - Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. This study reports that remdesivir at nanomolar concentrations inhibits carboxylesterase-2 (CES2) through covalent modifications. CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.

• Might proton pump or sodium-hydrogen exchanger inhibitors be of value to ameliorate SARs-CoV-2 pathophysiology? - Discovering therapeutics for COVID-19 is a priority. Besides high-throughput screening of compounds, candidates might be identified based on their known mechanisms of action and current understanding of the SARs-CoV-2 life cycle. Using this approach, proton pump (PPIs) and sodium-hydrogen exchanger inhibitors (NHEIs) emerged, because of their potential to inhibit the release of extracellular vesicles (EVs; exosomes and/or microvesicles) that could promote disease progression, and to directly...

• Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS-CoV-2 in the respiratory tract - As the death toll of Coronavirus disease 19 (COVID-19) continues to rise worldwide, it is imperative to explore novel molecular mechanisms for targeting SARS-CoV-2. Rather than looking for drugs that directly interact with key viral proteins inhibiting its replication, an alternative and possibly add-on approach is to dismantle the host cell machinery that enables the virus to infect the host cell and spread from one cell to another. Excellent examples of such machinery are host cell proteases...

• Spatial and temporal roles of SARS-CoV PL(pro) -A snapshot - SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CL^(pro) ) and papain-like protease (PL^(pro) ) into 16 nonstructural proteins (nsps). PL^(pro) is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in...

• Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin - The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here,...

• Therapeutic Approach Against 2019-nCoV by Inhibition of the ACE-2 receptor - The continued spread of the 2019 novel coronavirus (2019-nCoV) has prompted global concern. The formal name given to 2019-nCoV by the World Health Organization is COVID-19, while the International Committee on Taxonomy has named it severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to this viral attack, nations around the world have issued lockdown restrictions. Presently, there is no effective way to control the spread of 2019-nCoV, except through social distancing and hygienic...

• Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic - Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in Coronavirus Disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrate that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.

• A Review of Treatment of Coronavirus Disease 2019 (COVID-19): Therapeutic Repurposing and Unmet Clinical Needs - For the initial phase of pandemic of coronavirus disease 2019 (COVID-19), repurposing drugs that in vitro inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been attempted with overlooked or overestimated efficacy owing to limited clinical evidence. Most early clinical trials have the defects of study design, small sample size, non-randomized design, or different timings of treatment initiation. However, well-designed studies on asymptomatic or mild, or pediatric cases of...

• Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay - COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 virus with important political, socio-economic, and public health consequences. Inhibiting replication represents an important antiviral approach, and in this context two viral proteases, the SARS-CoV-2 main and papain-like proteases (PL^(pro)), which cleave pp1a and pp1ab polypeptides, are critical. Along with protease activity, the PL^(pro) possesses deubiquitinating activity, which is important in immune regulation. Naphthalene-based...

• Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics - The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus...

• Computational and Network Pharmacology Analysis of Bioflavonoids as Possible Natural Antiviral Compounds in Covid-19 - Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15...

• A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein - The COVID-19 pandemic caused by novel SARS-CoV-2 has resulted in an unprecedented loss of lives and economy around the world. In this study, search for potential inhibitors against two of the best characterized SARS-CoV-2 drug targets: S1 glycoprotein receptor-binding domain (RBD) and main protease (3CL^(Pro)), was carried out using the soy cheese peptides. A total of 1,420 peptides identified from the cheese peptidome produced using Lactobacillus delbrueckii WS4 were screened for antiviral...

From Patent Search

• Covid 19 - Chewing Gum - - link

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

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

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

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

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

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

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

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

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