Background Induction of labour (IOL) is one of the most commonly performed interventions in maternity care, with outpatient cervical ripening increasingly offered as an option for women undergoing IOL. The COVID-19 pandemic has changed the context of practice and the option of returning home for cervical ripening may now assume greater significance. This work aimed to examine whether and how the COVID-19 pandemic has changed practice around IOL in the UK. Method We used an online questionnaire to survey senior obstetricians and midwives at all 156 UK NHS Trusts and Boards that currently offer maternity services. Responses were analysed to produce descriptive statistics, with free text responses analysed using a conventional content analysis approach. Findings Responses were received from 92 of 156 UK Trusts and Boards, a 59% response rate. Many Trusts and Boards reported no change to their IOL practice, however 23% reported change in methods used for cervical ripening; 28% a change in criteria for home cervical ripening; 28% stated that more women were returning home during cervical ripening; and 24% noted changes to womens response to recommendations for IOL. Much of the change was reported as happening in response to attempts to minimise hospital attendance and restrictions on birth partners accompanying women. Conclusions The pandemic has changed practice around induction of labour, although this varied significantly between NHS Trusts and Boards. There is a lack of formal evidence to support decision-making around outpatient cervical ripening: the basis on which changes were implemented and what evidence was used to inform decisions is not clear.
Objective To determine the prevalence of olfactory dysfunctions, mainly, anosmia and to identify its associated factors in patients with COVID-19 infection. Study design A hospital-based prospective observational cohort study Setting A COVID dedicated hospital, Square Hospitals Ltd., Dhaka, Bangladesh. Methods We collected patients information including laboratory-confirmed COVID-19 test results. We used Pearson Chi-square test and logistic regression model to assess the associations between demographic and clinical characteristics and olfactory outcomes. Results Out of 600 COVID-19 positive patients, 38.7% were diagnosed with olfactory dysfunction. Our analyses showed that patients age, smoking status, cough, dyspnea, sore throat, asthenia, and nausea or vomiting were significantly associated with the anosmia. We observed the risk of developing anosmia was greater in younger patients than in older patients, and this risk decreased as age increased [odds ratio (OR) range for different age groups: 1.26 to 1.08]. Smoking patients were 1.73 times more likely to experience anosmia than non-smoking patients [OR=1.73, 95% confidence interval (CI) = 1.01-2.98]. In addition, patients complained asthenia had a significantly double risk of developing the anosmia [OR = 1.96, CI = 1.23-3.06]. Conclusions Our study shows that about 39% of patients diagnosed with olfactory dysfunction. Patients age, smoking status, and asthenia are significantly positively associated with the anosmia. Since anosmia can be a significant marker for the diagnosis of COVID-19, we suggest regular screening of olfactory dysfunction in patients with early symptoms of COVID-19, particularly younger patients, smoker, and complained asthenia.
As the COVID-19 pandemic drags into its second year, there is hope on the horizon, in the form of SARS-CoV-2 vaccines which promise disease elimination and a return to pre-pandemic normalcy. In this study we critically examine the basis for that hope, using an epidemiological modeling framework to establish the link between vaccine characteristics and effectiveness in bringing an end to this unprecedented public health crisis. Our findings suggest that vaccines that do not prevent infection will allow extensive endemic SARS-CoV-2 spread upon a return to pre-pandemic social and economic conditions. Vaccines that only reduce symptomatic COVID-19 or mortality will fail to mitigate serious COVID-19 mortality risks, particularly in the over-65 population, likely resulting in hundreds of thousands of US deaths on a yearly basis. Our modeling points to the possibility of complete SARS-CoV-2 elimination with high population-level compliance and a vaccine that is highly effective at reducing SARS-CoV-2 infection. Notably, vaccine-mediated reduction of transmission is critical for elimination, and in order for partially-effective vaccines to play a positive role in SARS-CoV-2 elimination, other stackable (complementary) interventions must be deployed simultaneously.
Comparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the recent average, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no central, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 77 countries, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in the worst-affected countries the annual mortality increased by over 50%, while in several other countries it decreased by over 5%, presumably due to lockdown measures decreasing the non-COVID mortality. Moreover, we found that while some countries have been reporting the COVID-19 deaths very accurately, many countries have been underreporting their COVID-19 deaths by an order of magnitude or more. Averaging across the entire dataset suggests that the world9s COVID-19 death toll may be at least 1.6 times higher than the reported number of confirmed deaths.
Contact tracing in the UK for Covid-19 is performed by NHS Test and Trace (NHSTT) via telephone or email. This study estimates how many patients who have been admitted to hospital are not reached by NHSTT and the number of their contacts who were not advised to self-isolate. Medical Student volunteers conducted face to face interviews with patients diagnosed with Covid-19 on an infectious diseases ward. Data on their close contacts were sent to NHSTT. 20 cases were enrolled. 13(65%) did not engage with NHSTT, 4(20%) because they had no positive PCR, 9(45%) because of severity of illness, language or intellectual difficulties. 49 close contacts were identified of whom 33(67%) were from cases who had not engaged with NHSTT. Backwards contacts tracing information was collected from 11(55%) cases and 8(40%) gave detailed information. These data suggest that NHSTT fails to engage nearly two thirds of Covid-19 in-patients and fails to advise two thirds of their close contacts to self isolate. Volunteers used face to face interviews to overcome false negative tests, illness and communication problems to identify both close contacts and data on sources of infection.
Immune responses against SARS-CoV-2 have been vigorously analyzed. It has been proposed that a subset of mild or asymptomatic cases with undetectable antibodies may clear the virus in a T-cell cytotoxic-dependent manner, albeit recent data revealed the importance of B-cells in that regard. We hypothesized that underdiagnosed antigenemia/viremia may conceal humoral response possibly through immunocomplex formation. We report the first case of late-onset seroconversion detected following decline in antigenemia/viremia levels. Consequently, classification of at least a subset of COVID-19 cases as non-responders might not represent a true immunobiological phenomenon, rather reflect antibody masking due to prolonged antigenemia/viremia.
Background BNT162b2 vaccines showed high efficacy against COVID-19 in a randomized controlled phase-III trial. A vaccine effectiveness evaluation in real life settings is urgently needed, especially given the global disease surge. Hence, we assessed the short-term effectiveness of the first dose of BNT162b2-vaccine against SARS-CoV-2 infection. Given the BNT162b2 Phase-III results, we hypothesized that the cumulative incidence of SARS-CoV-2 infection among vaccinees will decline after 12 days following immunization compared to the incidence during the preceding days. Methods We conducted a retrospective cohort study using data from 2.6 million-member state-mandated health provider in Israel. Study population consisted of all members aged 16 or above years who were vaccinated with BNT162b2-vaccine between December/19/2020 and January/15/2021. We collected information regarding medical history and positive SARS-CoV-2 polymerase chain reaction test from days after first dose to January/17/2021. Daily and cumulative infection rates in days 13-24 were compared to days 1-12 after first dose using Kaplan-Meier survival analysis and generalized linear models. Findings Data of 503,875 individuals (mean age 59.7 years SD=14.7, 47.8% males) were analyzed, of whom 351,897 had 13-24 days of follow-up. The cumulative incidence of SARS-CoV-2 infection was 0.57% (n=2484) during days 1-12 and 0.27% (n=614) in days 13-24. A 51.4% relative risk reduction (RRR) was calculated in weighted-average daily incidence of SARS-CoV-2 infection from 43.41-per-100,000(SE=12.07) in days 1-12 to 21.08-per-100,000(SE=6.16) in days 13-24 following immunization. The decrement in incidence was evident from day 18 after first dose. Similar RRRs were calculated in individuals aged 60 or above (44.5%), younger individuals (50.2%), females (50.0%) and males (52.1%). Findings were similar in sub-populations and patients with various comorbidities. Conclusions We demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection.
Several new variants of the SARS-CoV-2 have been isolated in the United States, Mexico, and Canada. Many of the variants contain single variants of functional significance (e.g. S: N501Y increases transmissibility). To study the occurrence and co-circulation of these variants, we have developed an easy-to-use dashboard at https://janieslab.github.io/sars-cov-2.html. We created a multiple sequence alignment workflow and processing script to generate a variant dataset, which populates this dashboard. We then use the features of the dashboard, such as visualization of the single and complex nucleotide variants geospatially and in a color-coded matrix format. Users also interact with the dashboard to filter the underlying data to regions of interest and or variants of interest. The user can export reports based on the desired filters, which we intend to be used for regionally specific pandemic response. We find in Genbank, an isolate from Massachusetts containing [(S: Q677H), (ORF3a: Q57H), (M: A85S), (N: D377Y)] collected on September 11, 2020. Moreover, we find that many viral isolates bear a marker of increased transmissibility (S: N501Y) in linkage with at least one variant of concern isolated from Ohio also range across the Untied States and stretch from British Columbia, Canada to Mexico. When we analyze co-circulation of more complex variant constellations with (S: N501Y), we note that the Upper Midwest and Northeast United States contain these isolates. In summary, the viral variants that have raised concern in a few US States in recent reports are widespread. Based on the increase in the proportion of variant viruses being sampled and some empirical evidence in the United Kingdom, South Africa, and Ohio, these variants are likely to lead to increased transmission of SARS-CoV-2 across North America in the coming months.
Objective We aimed to explore the association of COVID-19 incidence with mental health in 225 team and staff members of five professional Austrian Football clubs captured by objective (location variance) or subjective (self-reported sleep quality, level of recovery, perceived risk of infection) mental health proxies. Methods Data collected during the implementation of a novel monitoring concept to enable safe continuation of professional Football during the COVID-19 pandemic were matched with Austrian COVID-19 incidence data and smartphone collected location data (time-period June 17th to July 31st, 2020). Multivariable linear regression models explored the association of COVID-19 incidence, defined as daily novel or active cases of COVID-19, with the objective and subjective health proxies while adjusting for the occurrence of one COVID-19 case in a staff member in one of the clubs, team status (i.e. player vs staff) and game days. Results Data from 115 participants were analysed. An increasing number of novel COVID-19 cases was significantly associated with deteriorating sleep quality (B 0.48, 95% CI 0.05; 1.00) but with none of the other mental health proxies. An increasing number of active COVID-19 cases was significantly associated with an increase in perceived infection risk (B 0.04, 95% CI 0.00; 0.07) and location variance (B 0.28, 95% CI 0.06; 0.49). Conclusion The adverse association of an increasing COVID-19 incidence with mental health in professional Footballers and staff members became obvious particularly in subjectively measured mental health. During the ongoing pandemic, targeted mental care should be included in the daily routines of this population.
Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ~25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed de novo following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.
Objective: COVID-19 has emerged as a global pandemic, affecting nearly 80 million people from 218 countries as of December 2020. At the same time, vitamin D deficiency seems to be prevalent among COVID-19 patients. Hence, the association between the prevalence of vitamin D deficiency and COVID-19 infection and mortality among European countries was examined. Design: A case series and recent literature review study Settings: Information on prevalence of vitamin D deficiency in each country was retrieved through literature searching on PubMed database. As of December, 23rd 2020, COVID-19 infections and mortalities per million population were extracted from the Worldometer website, whereas the latitude of each country was taken from the CSGNetwork website. The association between both vitamin D deficiency and COVID-19 infection and mortality were explored using correlation coefficients and scatterplots. Participants: European Countries-Populations Results: The range of prevalence of vitamin D deficiency among European countries was 6.9-75.1%, with most countries facing more than 50% of vitamin D deficiency among their population. Significant positive correlations were observed between COVID-19 infections (r=0.82; p<0.001) and mortalities (r=0.53; p=0.05) per million population with the prevalence of vitamin D deficiency. Most of the high latitude countries showed lower rates of COVID-19 infections and mortalities compared to middle latitude countries. Conclusion: Prevalence of vitamin D deficiency was significantly associated with both infection and mortality rate of COVID-19 among European countries. Thus, it is an important parameter to be considered when implementing preventive measures to mitigate the mortality rate of COVID-19.
OBJECTIVE: Neurological complications can worsen outcomes in COVID-19. We defined the prevalence of a wide range of neurological conditions among patients hospitalized with COVID-19 in geographically diverse multinational populations. METHODS: Using electronic health record (EHR) data from 348 participating hospitals across 6 countries and 3 continents between January and September 2020, we performed a cross-sectional study of hospitalized adult and pediatric patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test, both with and without severe COVID-19. We assessed the frequency of each disease category and 3-character International Classification of Disease (ICD) code of neurological diseases by countries, sites, time before and after admission for COVID-19, and COVID-19 severity. RESULTS: Among the 35,177 hospitalized patients with SARS-CoV-2 infection, there was increased prevalence of disorders of consciousness (5.8%, 95% confidence interval [CI]: 3.7%-7.8%, pFDR<.001) and unspecified disorders of the brain (8.1%, 95%CI: 5.7%-10.5%, pFDR<.001), compared to pre-admission prevalence. During hospitalization, patients who experienced severe COVID-19 status had 22% (95%CI: 19%-25%) increase in the relative risk (RR) of disorders of consciousness, 24% (95%CI: 13%-35%) increase in other cerebrovascular diseases, 34% (95%CI: 20%-50%) increase in nontraumatic intracranial hemorrhage, 37% (95%CI: 17%-60%) increase in encephalitis and/or myelitis, and 72% (95%CI: 67%-77%) increase in myopathy compared to those who never experienced severe disease. INTERPRETATION: Using an international network and common EHR data elements, we highlight an increase in the prevalence of central and peripheral neurological phenotypes in patients hospitalized with SARS-CoV-2 infection, particularly among those with severe disease.
Host genetics is an emerging theme in COVID-19 and few common polymorphisms and some rare variants have been identified, either by GWAS or candidate gene approach, respectively. However, an organic model is still missing. Here, we propose a new model that takes into account common and rare germline variants applied in a cohort of 1,300 Italian SARS-CoV-2 positive individuals. Ordered logistic regression of clinical WHO grading on sex and age was used to obtain a binary phenotypic classification. Genetic variability from WES was synthesized in several boolean representations differentiated according to allele frequencies and genotype effect. LASSO logistic regression was used for extracting relevant genes. We defined about 100 common driver polymorphisms corresponding to classical -threshold model-. Extracted genes were demonstrated to be gender specific. Stochastic rare more penetrant events on about additional 100 extracted genes, when occurred in a medium or severe background (common within the family), simulate Mendelian inheritance in 14% of subjects (having only 1 mutation) or oligogenic inheritance (in 10% having 2 mutations, in 11% having 3 mutations, etc). The combined effect of common and rare results can be described as an integrated polygenic score computed as: (nseverity-nmildness) +F (mseverity-mmildness) where n is the number of common driver genes, m is the number of driver rare variants and F is a factor for appropriately weighing the more powerful rare variants. We called the model -post-Mendelian-. The model well describes the cohort, and patients are clustered in severe or mild by the integrated polygenic scores, the F factor being calibrated around 2, with a prediction capacity of 65% in males and 70% in females. In conclusion, this is the first comprehensive model interpreting host genetics in a holistic post-Mendelian manner. Further validations are needed in order to consolidate and refine the model which however holds true in thousands of SARS-CoV-2 Italian subjects.
Coronavirus Disease 2019 (COVID-19) pandemic has become the greatest threat to global health in only a matter of months. Iran struggling with COVID-19 coincidence with Nowruz vacations has led to horrendous consequences for both people and the public health workforce. Modeling approaches have been proved to be highly advantageous in taking appropriate actions in the early stages of the pandemic. To this date, no study has been conducted to model COVID-19 to investigate the impact of disease factors, especially after travel restrictions in Iran. In this study, we exploited the opportunities that Artificial neural networks offer to investigate contributing factors of early-stage coronavirus spread via generating a model to predict daily confirmed cases in Iran. We collected publicly available data of confirmed cases in 24 provinces from April 4, 2020, to May 2, 2020, with a list of explanatory factors. The factors were checked separately for any linear associations and to train and validate a multilayer perceptron network. The accuracy of the models was evaluated, the R2 scores were 0.842 for population distribution, 0.822 for health index, and 0.864 for the population in the provinces. Our results suggest the significant impact of the mentioned factors on disease spread in the time of travel restrictions when the vacation ended. Accordingly, this information can be implicated in assessing the risk of epidemics and future policy makings in this area.
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
Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition: Covid19
Interventions: Drug: Placebo; Drug: Fluvoxamine
Sponsor: SigmaDrugs Research Ltd.
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
The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial) - Condition: Covid19
Interventions: Drug: Ivermectin 0.6mg/kg/day; Drug: Ivermectin 1.0mg/kg/day; Drug: Placebo; Drug: Hydroxychloroquine
Sponsor: Corpometria Institute
Not yet recruiting
APT™ T3X on the COVID-19 Contamination Rate - Condition: COVID-19
Interventions: Drug: Tetracycline hydrochloride 3%; Drug: Placebo
Sponsors: University of Nove de Julho; Santa Casa de Misericórdia de Porto Alegre
Not yet 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
COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition: Covid19
Interventions: Biological: Omalizumab; Other: Placebo
Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Not yet recruiting
Clinical Experimentation With Tenofovir Disoproxyl Fumarate and Emtricitabine for COVID-19 - Condition: Covid19
Interventions: Drug: Vitamin C 500 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG Oral Tablet; Drug: Tenofovir disoproxyl fumarate 300 MG plus emtricitabine 200 MG Oral Tablet
Sponsors: Universidade Federal do Ceara; Conselho Nacional de Desenvolvimento Científico e Tecnológico; São José Hospital for Infectious Diseases - HSJ; Central Laboratory of Public Health of Ceará - Lacen-CE
Recruiting
Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 - Condition: COVID-19
Interventions: Drug: Doxycycline Tablets; Drug: Rivaroxaban 15Mg Tab; Combination Product: Hydroxychloroquine and Azithromycin
Sponsor: Yaounde Central Hospital
Recruiting
Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Biological: Placebo
Sponsors: Jiangsu Province Centers for Disease Control and Prevention; West China Hospital
Not yet recruiting
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
COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition: Covid19
Intervention: Other: Specimens specific for the study
Sponsor: Hopital Foch
Recruiting
Early Use of Hyperimmune Plasma in COVID-19 - Condition: Covid19
Intervention: Other: hyperimmune plasma
Sponsors: Catherine Klersy; Policlinico San Matteo Pavia Fondazione IRCCS
Recruiting
Early Remdesivir Treatment in Covid-19: Why Wait Another Day? - Antiviral drug efficacy commonly depends on how soon after the onset of the infection is the treatment initiated. For COVID-19 there are no studies available to establish the benefit of early initiation of antivirals on patient outcomes. Remdesivir, an inhibitor of SARS-CoV-2 viral replication, was approved for the treatment of COVID-19 in patients requiring hospitalization. However, studies leading to its approval were conducted in COVID-19 patients with lower respiratory tract infection and/or...
Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells - An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung...
Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis - In the end of 2019 COVID-19 emerged as a new threat worldwide and this disease present impaired immune system, exacerbated production of inflammatory cytokines, and coagulation disturbs. Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have emerged as a therapeutic option due to its intrinsic properties to alleviate inflammatory responses, capable to promote the restoring of injured tissue. EVs contain heterogeneous cargo, including active microRNAs, small noncoding sequences...
A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication - Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (M^(pro)). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC(50) values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h,...
Anti-inflammatory potential of Quercetin in COVID-19 treatment - SARS-CoV-2 is a betacoronavirus causing severe inflammatory pneumonia, so that excessive inflammation is considered a risk factor for the disease. According to reports, cytokine storm is strongly responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Phylogenetic findings show more similarity of the SARS-CoV-2 virus with bat coronaviruses,...
The direct evidence and mechanism of traditional Chinese medicine treatment of COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing serious human disease to spread across the world in the past 20 years, after SARS and Middle East respiratory syndrome. As of mid-September 2020, more than 200 countries and territories have reported 30 million cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, including 950,000 deaths. Supportive treatment remains the mainstay of therapy for COVID-19. The World Health Organization...
Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients - CONCLUSION: These data suggest the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.
Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2 - Effective treatment or vaccine is not yet available for combating SARS coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic. Recent studies showed that two drugs, Camostat and Nafamostat, might be repurposed to treat COVID-19 by inhibiting human TMPRSS2 required for proteolytic activation of viral spike (S) glycoprotein. However, their molecular mechanisms of pharmacological action remain unclear. Here, we perform molecular dynamics simulations to investigate their native binding sites...
Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium - The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required...
Targeting novel structural and functional features of coronavirus protease nsp5 (3CL(pro), M(pro)) in the age of COVID-19 - Coronavirus protease nsp5 (M(pro), 3CL(pro)) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a...
Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids - Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A,...
Altered high-density lipoprotein composition and functions during severe COVID-19 - Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated...
Phenylbenzopyrone of flavonoids as a potential scaffold to prevent SARS-CoV-2 replication by inhibiting its MPRO main protease - CONCLUSION: The present study displaying flavonoids, possessing a potential scaffold for inhibiting main protease activity for all betacoronavirus is an attempt to provide new and safe drug leads within a reasonably short period.
Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188 - Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M^(pro)) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M^(pro), and provides an initial scaffold for the...
Molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT-IR, FT-Raman), drug likeness and molecular docking of the novel anti COVID-2 molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide (Dimer) - quantum chemical approach - Prospective antiviral molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been probed using Fourier transform infrared (FTIR), FT-Raman and quantum chemical computations. The geometry equilibrium and natural bond orbital analysis have been carried out with density functional theory employing Becke, 3-parameter, Lee-Yang-Parr method with the 6-311G++(d,p) basis set. The vibrational assignments pertaining to different modes of vibrations have been augmented by...
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.
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.
Seil-Haltevorrichtung (1)
mit einer Seil-Klemmeinrichtung (3), die auf dem Träger (2) angeordnet ist.
A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link
Covid 19 - Chewing Gum - - 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
Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.