Scientists and public were alarmed at first viral variant of SARS-CoV2 reported in December 2020. We have followed time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries. We examined complete SARS-CoV-2 nucleotide sequences in GISAID with sampling extending until January 20, 2021. These sequences originated from ten different countries: United Kingdom, South Africa, Brazil, USA, India, Russia, France, Spain, Germany, and China. Among the novel mutations, some previously reported mutations waned and some of them increased over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS-CoV-2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests.
We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatiotemporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals9 degree (number of social contacts) and total social proximity time is significantly more effective than the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result in reducing an additional 56−110k infections, 3.2− 5.4k hospitalizations, and 700−900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3−6 million fewer infections, 181−306k fewer hospitalizations, and 51−62k fewer deaths compared to age-based allocation. The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.
Objective: To investigate the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay. Methods: Serological testing was conducted on 708 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. Results: SARS-CoV-2 seroprevalence was 63.4% (449/708; 95% CI 59.8%-66.9%) using the BioMedomics assay and 71.9% (509/708; 95% CI 68.5%-75.1%) using the Elecsys assay. There were 62 discordant results between the two assays. One specimen was seropositive in the BioMedomics assay, but seronegative in the Elecsys assay, while 61 specimens were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Positive, negative, and overall percent agreements between the two assays were 88.0% (95% CI 84.9%-90.6%), 99.5% (95% CI 97.2%-99.9%), and 91.2% (95% CI 88.9%-93.1%), respectively, with a Cohen kappa of 0.80 (95% CI 0.77-0.83), indicating excellent agreement. Excluding specimens with lower antibody titers, the agreement improved with positive, negative, and overall percent concordance of 91.2% (95% CI 88.2%-93.6%), 99.5% (95% CI 97.2%-99.9%), and 93.9% (95% CI 91.7%-95.5%), respectively, and a Cohen kappa of 0.87 (95% CI 0.84-0.89). Logistic regression confirmed better agreement with higher antibody titers. Conclusion: The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated excellent performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and possible vaccine prioritization.
Background Early prediction of symptoms and mortality risks for COVID-19 patients would improve healthcare outcomes, allow for the appropriate distribution of healthcare resources, reduce healthcare costs, aid in vaccine prioritization and self-isolation strategies, and thus reduce the prevalence of the disease. Such publicly accessible prediction models are lacking, however. Methods Based on a comprehensive evaluation of existing machine learning (ML) methods, we created two models based solely on the age, gender, and medical histories of 23,749 hospital-confirmed COVID-19 patients from February to September 2020: a symptom prediction model (SPM) and a mortality prediction model (MPM). The SPM predicts 12 symptom groups for each patient: respiratory distress, consciousness disorders, chest pain, paresis or paralysis, cough, fever or chill, gastrointestinal symptoms, sore throat, headache, vertigo, loss of smell or taste, and muscular pain or fatigue. The MPM predicts the death of COVID-19-positive individuals. Results The SPM yielded ROC-AUCs of 0.53-0.78 for symptoms. The most accurate prediction was for consciousness disorders at a sensitivity of 74% and a specificity of 70%. 2440 deaths were observed in the study population. MPM had a ROC-AUC of 0.79 and could predict mortality with a sensitivity of 75% and a specificity of 70%. About 90% of deaths occurred in the top 21 percentile of risk groups. To allow patients and clinicians to use these models easily, we created a freely accessible online interface at www.aicovid.org. Conclusions The ML models predict COVID-19-related symptoms and mortality using information that is readily available to patients as well as clinicians. Thus, both can rapidly estimate the severity of the disease, allowing shared and better healthcare decisions with regard to hospitalization, self-isolation strategy, and COVID-19 vaccine prioritization in the coming months.
Detail is a double edged sword in epidemiological modelling. The inclusion of mechanistic detail in models of highly complex systems has the potential to increase realism, but it also increases the number of modelling assumptions, which become harder to check as their possible interactions multiply. Knock et al (2020) fit an age structured SEIR model with added health service compartments to data on deaths, hospitalization and test results from Covid-19 in seven English regions for the period March to December 2020. The simplest version of the model has 684 states per region. One main conclusion is that only full lockdowns brought the pathogen reproduction number, R, below one, with R >> 1 in all regions on the eve of March 2020 lockdown. We critically evaluate the Knock et al. epidemiological model, and the semi-causal conclusions made using it, based on an independent reimplementation of the model designed to allow relaxation of some of its strong assumptions. In particular, Knock et al. model the effect on transmission of both non-pharmaceutical interventions and weather using a piecewise linear function, b(t), with 12 breakpoints at selected government announcement or intervention dates. We replace this representation by a smoothing spline with time varying smoothness, thereby allowing the form of b(t) to be substantially more data driven. We conclude that there is no sound basis for using the Knock et al. model and their analysis to make counterfactual statements about the number of deaths that would have occurred with different lockdown timings. However, if fits of this epidemiological model structure are viewed as a reasonable basis for inference about the time course of incidence and R, then without very strong modelling assumptions, the pathogen reproduction number was probably below one, and incidence in substantial decline, some days before either of the first two English national lockdowns. Of course this does not imply that lockdowns had no effect, but it does suggest that other non-pharmaceutical interventions (NPIs) were much more effective than Knock et al. imply.
Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19 - Condition: Covid19
Interventions: Biological: COVI-AMG; Drug: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms - Condition: Covid19
Interventions: Biological: COVI-AMG; Drug: Placebo
Sponsor: Sorrento Therapeutics, Inc.
Not yet recruiting
Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition: COVID-19
Interventions: Drug: AZD7442; Drug: Placebo
Sponsor: AstraZeneca
Not yet recruiting
TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition: Covid19
Intervention: Drug: Tocilizumab
Sponsor: FMH College of Medicine and Dentistry
Completed
Convalescent Plasma in the Treatment of Covid-19 - Condition: Covid19
Interventions: Biological: Convalescent plasma from COVID-19 donors; Biological: Placebo
Sponsors: Helsinki University Central Hospital; Finnish Red Cross
Recruiting
A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19 - Condition: Severe COVID-19
Interventions: Drug: VB-201 + Standard of care; Drug: Standard of care
Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
Recruiting
Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition: Covid-19
Intervention: Other: ivermectin impregnated mask
Sponsor: South Valley University
Recruiting
An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition: Covid19
Interventions: Drug: Ivermectin Tablets; Drug: Doxycycline Tablets; Drug: Placebo
Sponsor: Max Health, Subsero Health
Recruiting
CPI-006 Plus Standard of Care Versus Placebo Plus Standard of Care in Mild to Moderately Symptomatic Hospitalized Covid-19 Patients - Condition: Covid-19
Interventions: Drug: CPI-006 2 mg/kg + SOC; Drug: CPI-006 1 mg/kg + SOC; Drug: Placebo + SOC
Sponsor: Corvus Pharmaceuticals, Inc.
Recruiting
Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: FMH College of Medicine and Dentistry
Completed
Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition: Covid-19
Interventions: Drug: Famotidine; Drug: Placebo
Sponsors: Northwell Health; Cold Spring Harbor Laboratory
Recruiting
Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 - Conditions: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19
Interventions: Drug: SNG001; Drug: Placebo
Sponsor: Synairgen Research Ltd.
Recruiting
COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition: Covid19
Intervention: Other: Specimens specific for the study
Sponsor: Hopital Foch
Recruiting
Safety, Tolerability and Efficacy Of S-1226 in Moderate Severity Covid-19 Bronchiolitis/Pneumonia - Conditions: Covid19; SARS-CoV-2 Infection
Intervention: Drug: S-1226
Sponsor: SolAeroMed Inc.
Not yet recruiting
Restoration of Endothelial Integrity in Patients With COVID-19 (RELIC) - Condition: COVID-19
Intervention: Biological: Thawed plasma
Sponsor: University of Alabama at Birmingham
Not yet recruiting
Thrombin generation in patients with COVID-19 with and without thromboprophylaxis - CONCLUSIONS: COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.
PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia - BACKGROUND: Standard care in severe SARS-CoV-2 pneumonia complicated by severe dyspnea and respiratory failure, consists of symptom reduction, ultimately supported by mechanical ventilation. Patients with severe SARS-CoV-2, a prominent feature of COVID-19, show several similar symptoms to Critical Asthma Syndrome (CAS) patients, such as pulmonary edema, mucus plugging of distal airways, decreased tissue oxygenation, (emergent) exhaustion due to severe dyspnea and respiratory failure. Prior…
Immune Checkpoint Inhibition in COVID-19: Risks and Benefits - INTRODUCTION: Immune checkpoint inhibition (ICI) is a novel cancer immunotherapy, which is administered in patients with metastatic, refractory, or relapsed solid cancer types. From the initiation of the Corona Virus Disease 2019 (COVID-19) pandemic many studies reported a higher severity and mortality rate of COVID-19 among patients with cancer in general.
In silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19 - Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of…
Structural basis for the inhibition of the SARS-CoV-2 main protease by the anti-HCV drug narlaprevir - No abstract
Potent and Selective Knockdown of Tyrosine Kinase 2 by Antisense Oligonucleotides - Tyrosine kinase 2 (TYK2) is a member of the JAK family of nonreceptor tyrosine kinase, together with JAK1, JAK2, and JAK3. JAKs are important signaling mediators of many proinflammatory cytokines and represent compelling pharmacological targets for autoimmune and inflammatory diseases. Pan-acting small-molecule JAK inhibitors were approved for the treatment of rheumatoid arthritis and ulcerative colitis. However, their limited selectivity among JAK members have led to undesirable side effects,…
A Neutralization Assay Based on Pseudo-Typed Lentivirus with SARS CoV-2 Spike Protein in ACE2-Expressing CRFK Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic zoonotic virus that spreads rapidly. In this work, we improve the hitherto existing neutralization assay system to assess SARS-CoV-2 inhibitors using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein (LpVspike +) and angiotensin-converting enzyme 2 (ACE2)-transfected cat Crandell-Rees feline kidney (CRFK) cells as the host cell line. Our method was 10-fold more sensitive compared to the typical…
Mechanisms of Coronavirus Nsp1-Mediated Control of Host and Viral Gene Expression - Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three…
SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study - The coronavirus disease (COVID-19) is spreading between human populations mainly through nasal droplets. Currently, the vaccines have great hope, but it takes years for testing its efficacy in human. As there is no specific drug treatment available for COVID-19 pandemic, we explored in silico repurposing of drugs with dual inhibition properties by targeting transmembrane serine protease 2 (TMPRSS2) and human angiotensin-converting enzyme 2 (ACE2) from FDA-approved drugs. The TMPRSS2 and ACE2…
An Urgent Industrial Scheme both for Total Synthesis, and for Pharmaceutical Analytical Analysis of Umifenovir as an Anti-Viral API for Treatment of COVID-19 - CONCLUSION: The most important pharmaceutical analytical methods containing OVI test (mainly ethanol (about 171 ppm) much lower than the limits, by gas chromatography-Flame Ionization Detector (GC-FID) instrument), Assay content (about 99.6% by potentiometric titration), and related purity analysis (by High performance liquid chromatography-Ultraviolet Detector (HPLC-UV)) (about 99.8%) were performed and described to give a more clear industrial scheme.
Ethical Dilemma: An Unprecedented Strike by Health care Workers in Early February 2020 in Hong Kong - Urging the government to exercise a complete border closure to inhibit the spread of the novel coronavirus from Mainland China, about 8,000 health care workers participated in a 5-day strike in early February 2020 in Hong Kong. Despite gaining 61% support from the public, dissenters criticised that the participants violated professional ethics and abandoned their accountabilities, which led to moral distress. However, the participants were guided by the four fundamental medical principles…
Complement inhibition initiated recovery of a severe myasthenic crisis with COVID-19 - We report on a patient with refractory Myasthenia gravis with acetylcholine receptor antibodies with two prior myasthenic crises suffering from COVID-19 with rapid evolving weakness and respiratory failure. Respiratory failure developed and prolonged mechanical ventilation was necessary. After plasmapheresis, residual, severe generalized and bulbar weakness persisted. Complement inhibition with eculizumab was, therefore, introduced and lead to rapid recovery. In refractory myasthenic crisis…
Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study - A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness…
Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity - Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the…
SARS-CoV-2 recruits a haem metabolite to evade antibody immunity - The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of haem metabolism, with nanomolar affinity. Using cryo-electron microscopy and X-ray crystallography we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune…
SARS-CoV-2 antibodies - - link
SARS-CoV-2 antibodies - - link
A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - link
TREATMENT OF COVID-19 WITH REBAMIPIDE - - link
METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link
A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link
Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.
一种医用可佩戴式防护口鼻的微型气幕系统 - 本发明公开了一种医用可佩戴式防护口鼻的微型气幕系统,包括框柱,框柱一侧开凿有气幕送风口和呼吸用送风口,气幕送风口和呼吸用送风口内分别连接有软管一和软管二,框柱内开凿有水平条缝和垂直条缝,水平条缝与垂直条缝均与气幕送风口相连通,框柱靠近水平条缝的一侧贯穿开凿有出风口,出风口内设有滤网,出风口贯穿框柱的一端连接有高效过滤器,滤网与高效过滤器之间连接有吸气泵,框柱靠近出风口的一侧连接有电池和开关。本发明通过提出一种在口腔处应用洁净空气幕阻挡气溶胶传播的可佩戴装置,可以在口腔类相关诊疗过程,保护医生和周围人的健康,避免引起可能引发的呼吸道疾病交叉感染。 - link
COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link
Vorrichtung (10) umfassend einen Schutzschirm (12) und einen Filter (14) zum Herausfiltern von Viren (16) aus einem Schall erzeugenden Luftstrom (18), der von einem Musiker (20) beim Musizieren mit einem Musikinstrument oder beim Singen erzeugt wird, wobei der Schutzschirm (12) zur Verringerung des Risikos einer Infektion mit den Viren (16) dafür vorgesehen ist, wenigstens einen Teil der mit dem Luftstrom transportierten Viren (16) aufzufangen, der Schutzschirm (12) eine erste Seite (22) und eine zweite Seite (24) aufweist, die voneinander abgewandt sind, und der Schutzschirm (12) wenigstens einen sich von der ersten (22) bis zu der zweiten Seite (24) erstreckenden Durchlass (26) aufweist, wobei dieser Durchlass (26) zum Durchströmen mit wenigstens einem Teil des beim Musizieren erzeugten Luftstroms (18) vorgesehen ist und der Filter (14) zum Herausfiltern von Viren (16) aus dem Luftstrom (18) in dem Durchlass (26) des Schutzschirms (12) angeordnet ist.