CONQUEST (COroNavirus QUESTionnaire) is an online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. We analysed survey results from the start of the 2020/2021 academic year, prior to the second national lockdown (14/09/2020-01/11/2020), where COVID-19 outbreaks led to lockdown of some student halls of residence. The aim of these analyses was to enhance knowledge of student contact patterns to inform infection disease mathematical modelling approaches. Responses captured information on demographics, contacts on the previous day, symptoms and self-isolation during the prior week, and COVID-19 status. 740 students provided 1261 unique records. Of 42 (3%) students testing positive in the prior fortnight, 99% had been self-isolating. The median number of contacts on the previous day was 2 (interquartile range: 1-5), mode: 1, mean: 6.1; 8% had ≥20 contacts. 57% of student contacts were other UoB students/staff. Most students reported few daily contacts but there was heterogeneity, and some reported many. Around 40% of student contacts were with individuals not affiliated with UoB, indicating potential for transmission to non-students/staff.
SARS-CoV-2 is a respiratory virus supposed to enter the organism through aerosol or fomite transmission to the nose, eyes and oropharynx. It is responsible for various clinical symptoms, including hyposmia and other neurological ones. Current literature suggests the olfactory mucosa as a port of entry to the CNS, but how the virus reaches the olfactory groove is still unknown. Because the first neurological symptoms of invasion (hyposmia) do not correspond to first signs of infection, the hypothesis of direct contact through airborne droplets during primary infection and therefore during inspiration is not plausible. The aim of this study is to evaluate if a secondary spread to the olfactory groove in a retrograde manner during expiration could be more probable.
OBJECTIVES To develop and assess the performance of a system for shared ventilation that uses clinically available components to individualize tidal volumes under a variety of clinically relevant conditions. DESIGN Evaluation and in vitro validation study. SETTING Ventilator shortage during the SARS-CoV-2 global pandemic. PARTICIPANTS The design and validation team consisted of intensive care physicians, bioengineers, computer programmers, and representatives from the medtech sector. METHODS Using standard clinical components, a system of shared ventilation consisting of two ventilatory limbs was assembled and connected to a single ventilator. Individual monitors for each circuit were developed using widely available equipment and open source software. System performance was determined under 2 sets of conditions. First, the effect of altering ventilator settings (Inspiratory Pressure, Respiratory rate, I:E ratio) on the tidal volumes delivered to each lung circuit was determined. Second, the impact of altering the compliance and resistance in one simulated lung circuit on the tidal volumes delivered to that lung and the second lung circuit was determined. All measurements at each setting were repeated three times to determine the variability in the system. RESULTS The system permitted accurate and reproducible titration of tidal volumes to each lung circuit over a wide range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures stepwise from 4-20cm H2O, of respiratory rates from 6-20 breaths/minute and I:E ratio from 1:1 to 1:4 resulted in near identical tidal volumes delivered under each set of conditions to each simulated lung. Stepwise alteration of compliance and resistance in one test lung circuit resulted in reproducible alterations in tidal volume to the test lung, with little change to tidal volumes in the control lung (a change of only 6% is noted). All tidal volumes delivered were highly reproducible upon repetition. CONCLUSIONS We demonstrate the reliability of a simple shared ventilation system assembled using commonly available clinical components that allows individual titration of tidal volumes. This system may be useful as a temporary strategy of last resort where the numbers of patients requiring invasive mechanical ventilation exceeds supply of ventilators.
Aims To compare the risk of adverse outcomes (i.e. hospital/intensive care admission, death) in population sub-groups during two periods of the COVID-19 pandemic in the Republic of Ireland. Methods We analysed routinely-collected, publicly-available data on 67,900 people with laboratory confirmed COVID-19 infection between 29th Feb to 14th Nov 2020. This period encompassed two waves of infection and two corresponding national lockdowns. For two observational periods covering each wave (W1, W2), each ending 17-19 days before implementation of high-level national restrictions, we segmented the population based on age and underlying clinical conditions. Results The prevalence of laboratory confirmed COVID-19 was 1.4%. The risk of admission to hospital, admission to intensive care, and death was 7.2%, 0.9%, and 2.5%, respectively. Compared to younger confirmed cases, those aged ≥65 y had increased risk of hospital admission (RR 5.61), ICU admission (RR 3.56), and death (RR 60.8). W2 was associated with more cases and fewer adverse events than W1. The risk of all adverse outcomes was reduced in W2 than in W1. Conclusions Ongoing responses should consider the variation in risk of adverse outcomes between specific sub-groups. These findings indicate the need to sustain the prevention, identification and management of noncommunicable diseases to reduce the burden of COVID-19.
The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, existing metabolomics studies are either underpowered, measure only a restricted subset of metabolites (9targeted metabolomics9), compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model. We here provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict patient9s infection severity (i.e. mild or severe) and potential outcome (i.e. discharged or deceased). High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model. The predictors were selected for their relevant biological function and include cytosine (reflecting viral load), kynurenine (reflecting host inflammatory response), nicotinuric acid, and multiple short chain acylcarnitines (energy metabolism) among others. Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.
Objective Describe the clinical and respiratory characteristics of critical patients with coronavirus disease 2019 (COVID-19). Design Observational and retrospective study over 6 months. Setting Intensive care unit (ICU) of a high complexity hospital in Buenos Aires, Argentina. Patients Patients older than 18 years with laboratory-confirmed COVID-19 by reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 were included in the study. Variables of interest Demographic characteristics such as sex and age, comorbidities, laboratory results, imaging results, ventilatory mechanics data, complications, and mortality were recorded. Results A total of 168 critically ill patients with COVID-19 were included. 66% were men with a median age of 65 years (58-75. 79.7% had at least one comorbidity. The most frequent comorbidity was arterial hypertension, affecting 52.4% of the patients. 67.9 % required invasive mechanical ventilation (MV), and no patient was treated with non-invasive ventilation. Most of the patients in MV (73.7%) required neuromuscular blockade due to severe hypoxemia. 36% of patients were ventilated in the prone position. The length of stay in the ICU was 13 days (6-24) and the mortality in the ICU was 25%. Conclusions In this study of critical patients infected by SARS-CoV-2 in a high-complexity hospital, the majority were comorbid elderly men, a large percentage required invasive mechanical ventilation, and ICU mortality was 25%.
Background. SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 439000 confirmed cases as of September 1st, 2020. Aim. In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system. Methods. Patients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patient9s admission date. Results. As of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 - 21.1%), haematological and oncological diseases (3 - 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 - 55.2% in children), renal (681 - 25.7%) and cardiac (631 - 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults. Conclusion. The surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.
Background: Belgium has been struggling with a second pandemic wave caused by SARS-CoV-2. Aim: The goal of this study was to estimate rates of carriership and viral loads in the general population in order to evaluate the dynamics leading to the second wave. Methods: Since the major Antwerp hospitals implemented extensive (pre-)admission SARS-CoV-2 screening of patients (eg. prior to elective surgery), they have gathered valuable information regarding the viral prevalence, incidence, and viral loads in the general population throughout the pandemic period. Prevalences and incidences were calculated and compared with available governmental data (numbers of positively tested and contacted cases). Major government coronavirus responses were taken into account. Results: The overall positivity rate of (pre)admission screenings was 1.3% (35.4% of positive cases carrying high viral loads). The highest prevalence of carriership was found in the elderly (2.6% for +80 y). 0-18 year-olds tested positive in 0.9% of cases. We estimated that, by extrapolation of cohort data, 20.3 % of the Antwerp population contracted the virus, whereas only 3.0 % was tested positive. In September, restriction measures were eased at a time when increased incidences were being observed. Conclusion: The estimation that only a small proportion of the positive cases (including cases with high viral loads) was detected and traced, in combination with a country-wide easing of restriction measures within a period of increasing incidences (and within an overall high base-line prevalence of the virus), were, in our opinion, the major drivers in the origin of the second pandemic wave.
OBJECTIVES To investigate if COVID-19 convalescent plasma (CCP) transfusion in patients with severe respiratory failure will increase plasma levels of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody titers while improving survival and clinical outcomes. DESIGN Observational, retrospective, control study of anti-RBD of SARS-CoV-2 IgG and IgM titers from serial plasma samples drawn before and after CCP administration. Clinical improvement in CCP recipients is assessed and compared to COVID-19 control patients. SETTING Patients hospitalized with severe COVID19, United States, between April 17 and July 19, 2020 PARTICIPANTS 34 patients hospitalized with severe or life threatening COVID-19 and who consented and received a CCP transfusion, 95 control patients with COVID-19 not transfused with CCP. 34 out the 95 control patients were matched for age, sex, and the level of respiratory support required. Patients less than 18 years old were excluded. MAIN OUTCOME MEASURES Serial trends of anti-RBD of SARS-CoV-2 IgG and IgM titers in CCP recipients are compared to those in control patients. The primary outcome is survival at 30 days, and the secondary outcomes are length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital, and LOS in the ICU. RESULTS CCP transfusion occurred in 34 patients at a median of 11 days following COVID-19 symptom onset. Immediately prior to CCP transfusion, patients median SARS-CoV-2 IgG and IgM titers were 3200 (IQR, 50 to 9600) and 320 (IQR, 40 to 640) respectively. Following a Loess regression analysis, the kinetics and distribution of anti-RBD of SARS-CoV-2 IgG and IgM in plasma from CCP recipients were comparable to those from a control group of 68 patients who did not receive CCP. CCP recipients presented with similar survival, similar duration on ventilator and/or ECMO support, as well as ICU and hospital LOS, compared to a matched control group of 34 patients. CONCLUSION In the present study, hospitalized COVID-19 patients with severe respiratory failure transfused with CCP presented with high titers of SARS-CoV-2 IgG antibodies before transfusion and did not show improved survival at 30 days.
Approximately 20-40% of SARS-CoV-2 infection is asymptomatic; however, data are limited on drivers of such infection. Among over 730,000 SARS-CoV-2 test results in Los Angeles between August-October, 2020, we found heterogenous frequencies of asymptomatic infection among various sup-populations. Further research is needed to delineate drivers of asymptomatic SARS-CoV-2 infection.
BACKGROUND: Following COVID-19 exposure, the CDC recommends a 10-14 day quarantine for asymptomatic individuals and more recently a 7 day quarantine with a negative PCR test. We performed a university-based prospective student cohort study to determine if early PCR negativity predicts day 14 negativity. METHODS: We enrolled 101 asymptomatic, quarantining, students, performed nasopharyngeal swabs for viral testing on days 3 or 4, 5, 7, 10 and 14 and determined the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval. RESULTS: Overall, 14 of 90 (16%, 95% CI: 9% - 25%) tested positive while in quarantine, with 7 initial positive tests on day 3 or 4, 5 on day 5, 2 on day 7, and none on day 10 or 14. Rates of concordant negative test results are: day 5 vs. day 14 = 45/50 (90%, 95% CI: 78% - 97%); day 7 vs. day 14 = 47/52 (90%, 95% CI: 79% - 97%); day 10 vs. day 14 = 48/53 (91%, 95% CI:79% - 97%), with no evidence of different negative rates between earlier days and day 14 by McNemars test, p > 0.05. CONCLUSIONS: The 16% positive rate supports the ongoing need to quarantine close contacts of COVID-19 cases, but this prospective study provides the first direct evidence that exposed asymptomatic students ages 18-44 years in a university setting are at low risk if released from quarantine at 7 days if they test negative PCR test prior to release.
Background. When patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: Virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten the time to recovery, is contraindicated. Antiviral treatment with convalescent plasma could be an alternative treatment option. Methods. In this case series we present two kidney transplant recipients and two patients dependent on haemodialysis who were infected with SARS-CoV-2 and received convalescent plasma. Antibodies against the spike 1 protein of SARS-CoV-2 were determined sequentially by IgG ELISA and neutralization assay and specific T cell responses by interferon-gamma ELISpot. Results. Prior to treatment, in three patients antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers (≤ 1:40). One patient was also negative to the ELISpot and two showed weak responses. After convalescent plasma treatment we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific T cell responses. After intermittent clinical improvement one kidney transplant recipient again developed typical symptoms at day 12 after treatment and received a second cycle of convalescent plasma treatment. Altogether, three patients clinically improved and could be discharged from hospital. However, one multimorbid female in her early eighties deceased. Conclusions. Our data suggest that the success of convalescent plasma therapy may only be temporary in patients with chronic kidney disease; which requires an adaptation of the treatment regimen. Close monitoring after treatment is needed for this patient group.
BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 μg dose levels. BNT162b2 elicited strong antibody responses, with S-binding IgG concentrations above those in a COVID-19 human convalescent sample (HCS) panel. Day 29 (7 days post-boost) SARS-CoV-2 serum 50% neutralising geometric mean titers were 0.3-fold (1 μg) to 3.3-fold (30 μg) those of the HCS panel. The BNT162b2-elicited sera neutralised pseudoviruses with diverse SARS-CoV-2 S variants. Concurrently, in most participants, S-specific CD8+ and T helper type 1 (TH1) CD4+ T cells had expanded, with a high fraction producing interferon-γ (IFNγ). Using peptide MHC multimers, the epitopes recognised by several BNT162b2-induced CD8+ T cells when presented on frequent MHC alleles were identified. CD8+ T cells were shown to be of the early-differentiated effector-memory phenotype, with single specificities reaching 0.01-3% of circulating CD8+ T cells. In summary, vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19.
From 31.10. - 1.11. 2020 Slovakia has used the SD Biosensor Standard Q Ag-Test for nationwide tests for SARS-CoV-2, in which 3,625,332 persons from 79 counties were tested. Based on this data, we calculate that the specificity of the test is at least 99.6% (with a 97.5% one-sided lower confidence bound). Our analysis is based on a worst case approach in which all positives are assumed to be false positives. Therefore, the actual specificity is expected to exceed 99.6%.
INTRODUCTION - COVID-19 convalescent plasma (CCP) transfusion has emerged in the past months as an alternative approach to treat pneumonia cases of SARS-CoV-2. Current evidence regarding characteristics of the plasma product, the titer of neutralizing antibodies (nAbs) in the transfused units, time to onset of intervention, and impact of nAbs produced by the patient are limited and heterogeneous. MATERIAL AND METHODS - We describe the preliminary results of 104 patients with severe pneumonia due to SARS-CoV-2 transfused with CCP at three medical centers in Brazil. All enrolled patients were transfused with doses between 200 mL through 600mL of ABO compatible CCP on days 0-2 after enrolment. Clinical parameters were monitored and nAbs titration was performed using the cytopathic effect-based virus neutralization test with SARS-CoV-2 (GenBank MT126808.1). RESULTS - Forty-one patients achieved clinical improvement on day 14, and multivariable logistic regression showed that nAbs T (from CCP units transfused) (p=0.001), nAbs P0 (on day of enrolment) (p=0.009) and use of other supportive therapies (p<0.001) were associated with higher odds for this clinical improvement. Considering ICU length of stay (LOS) and length of mechanical ventilation, in our analysis, nAbs P0 were associated with a significant reduction in ICU LOS (p=0.018) and duration of mechanical ventilation (p<0.001). Administration of CCP after 10 days of symptom onset was associated with increases in ICU length of stay (p<0.001). DISCUSSION/CONCLUSION - Despite the study limitations, our data have shown an association between patients previously acquired nAbs and clinical outcomes. The potential value of timely administration of CCP transfusion before day 10 of disease onset was demonstrated and nAbsP0, but not nAbsT, were associated with ICU LOS, and duration of mechanical ventilation on the improvement of clinical outcomes was also demonstrated. In conclusion, we consider these data are useful parameters to guide future CPP transfusion strategies to COVID19.
Ivermectin for Severe COVID-19 Management - Condition: COVID-19
Intervention: Drug: Ivermectin
Sponsors: Afyonkarahisar Health Sciences University; NeuTec Pharma
Completed
Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19) - Condition: COVID-19
Interventions: Biological: Group A (AG0302-COVID19); Biological: Group A (Placebo); Biological: Group B (AG0302-COVID19); Biological: Group B (Placebo)
Sponsors: AnGes, Inc.; Japan Agency for Medical Research and Development
Recruiting
Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - - Condition: COVID-19
Interventions: Drug: Omegaven®; Drug: Sodium chloride
Sponsor: Karolinska University Hospital
Recruiting
Sarilumab Treatment In cytoKinE Storm Caused by Infection With COVID-19 - Condition: COVID-19 Drug Treatment
Intervention: Drug: Sarilumab
Sponsors: Clinica Universidad de Navarra, Universidad de Navarra; Sanofi; Hospital Universitario Infanta Leonor
Recruiting
The Protective Potential of Exercise Training on the Cardiopulmonary Morbidity After COVID-19 - Condition: COVID-19, SARS-CoV2
Interventions: Behavioral: High intensity interval training; Behavioral: Standard care
Sponsor: Rigshospitalet, Denmark
Not yet recruiting
The Efficacy, Safety and Immunogenicity Study of Inactivated SARS-CoV-2 Vaccine for Preventing Against COVID-19 - Condition: COVID-19
Interventions: Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell); Biological: Placebo
Sponsor: Chinese Academy of Medical Sciences
Not yet recruiting
Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial - Condition: Covid19
Interventions: Biological: SARS-CoV-2 convalescent plasma; Other: Standard of care
Sponsors: Joakim Dillner; Karolinska Institutet; Danderyd Hospital; Falu Hospital
Not yet recruiting
Efficacy and Safety of TY027, a Treatment for COVID-19, in Humans - Condition: Coronavirus Disease-2019 (COVID-19)
Interventions: Biological: TY027; Other: 0.9% saline
Sponsor: Tychan Pte Ltd.
Not yet recruiting
Use of BCG Vaccine as a Preventive Measure for COVID-19 in Health Care Workers - Condition: COVID 19 Vaccine
Intervention: Biological: BCG vaccine
Sponsors: Universidade Federal do Rio de Janeiro; Ministry of Science and Technology, Brazil
Recruiting
At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19 - Condition: Covid19
Intervention: Drug: bamlanivimab
Sponsors: Daniel Griffin, MD PhD; Eli Lilly and Company; Optum, Inc.
Not yet recruiting
COVID-19 And Geko Evaluation: The CAGE Study - Condition: Covid19
Intervention: Device: geko T3
Sponsor: Lawson Health Research Institute
Not yet recruiting
A Study of FOY-305 in Patients With SARS-Cov-2 Infection (COVID-19) - Condition: SARS-CoV-2 Infection (COVID-19)
Interventions: Drug: FOY-305; Drug: Placebo
Sponsor: Ono Pharmaceutical Co. Ltd
Recruiting
A Clinical Safety Study on AT-100 in Treating Adults With Severe COVID-19 Infection - Condition: Covid19
Intervention: Biological: AT-100
Sponsor: Airway Therapeutics, Inc.
Not yet recruiting
LYT-100 in Post-acute COVID-19 Respiratory Disease - Condition: Covid19
Interventions: Drug: LYT-100; Other: Placebo
Sponsors: PureTech; Clinipace Worldwide; Novotech (Australia) Pty Limited
Not yet recruiting
WHO COVID-19 Solidarity Trial for COVID-19 Treatments - Condition: Covid19
Interventions: Drug: Remdesivir; Drug: Acalabrutinib; Drug: Interferon beta-1a; Other: Standard of Care
Sponsor: The University of The West Indies
Not yet recruiting
Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort - No abstract
Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies - CONCLUSION: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.
Natural Products Homoharringtonine and Emetine Alkaloids for SARSCoV-2 Treatment Options - CONCLUSION: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.
Protease-activated receptor 1 as a potential therapeutic target for COVID-19 - Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism…
Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific…
Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models - The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation…
Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures - The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense…
Ca (2+) -dependent mechanism of membrane insertion and destabilization by the SARS-CoV-2 fusion peptide - Cell penetration after recognition of the SARS-CoV-2 virus by the ACE2 receptor, and the fusion of its viral envelope membrane with cellular membranes, are the early steps of infectivity. A region of the Spike protein (S) of the virus, identified as the “fusion peptide” (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor binding domain of the Spike. Studies have shown that penetration is enhanced by the required binding of Ca…
Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms - SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo . Most notably the RNA polymerase targeting…
A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections - Background: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences. Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N1), HIV-1, and…
Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review - To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug…
Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro - The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-Cov and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, and facilitates the attachment of…
Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections - Zoonotic spillover, i.e. pathogen transmission from animal to human, has repeatedly introduced RNA viruses into the human population. In some cases, where these viruses were then efficiently transmitted between humans, they caused large disease outbreaks such as the 1918 flu pandemic or, more recently, outbreaks of Ebola and Coronavirus disease. These examples demonstrate that RNA viruses pose an immense burden on individual and public health with outbreaks threatening the economy and social…
Mechanistic Aspects and Therapeutic Potential of Quercetin against COVID-19-Associated Acute Kidney Injury - The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various…
Lectin Protein as a Promising Component to Functionalize Micelles, Liposomes and Lipid NPs against Coronavirus - The outbreak of a novel strain coronavirus as the causative agent of COVID-19 pneumonia, first identified in Wuhan, China in December 2019, has resulted in considerable focus on virulence abilities of coronavirus. Lectins are natural proteins with the ability to bind specific carbohydrates related to various microorganisms, including viruses, bacteria, fungi and parasites. Lectins have the ability to agglutinate and neutralize these pathogeneses. The delivery of the encapsulated antiviral agents…
“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.
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.
疫苗融合蛋白 - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。
AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -
一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法 - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。
柴胡解毒药物组合物及其制备方法和应用 - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡3060份，黄芩1530份，法半夏1530份，生姜1530份，大枣510份，枳实2040份，大黄1020份，桃仁1020份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。
一种新型冠状病毒RBD核苷酸序列、优化方法与应用 - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。
ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg
Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -
Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.
Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19 -
Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.