Offersenwilliamson8350

Results Eighty-four participants tested positive for SARS-CoV-2 antibodies. The HCW with a positive SARS-CoV-2 antibody result came from different parts of the city. The adjusted seroprevalence of SARS-CoV-2 antibodies was 12.3% [CI 9.0-15.7]. Using age-stratified infection fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence, the number of predicted deaths was 8 times the number of reported deaths. Conclusion The high seroprevalence of SARS-CoV-2 antibodies among HCW and the discrepancy in the predicted versus reported deaths, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spread by direct, indirect, or close contact with infected people via infected respiratory droplets or saliva. Crowded indoor environments with sustained close contact and conversations are a particularly high-risk setting.

We performed a meta-analysis through July 29, 2020 of SARS-CoV-2 household secondary attack rate (SAR), disaggregating by several covariates (contact type, symptom status, adult/child contacts, contact sex, relationship to index case, index case sex, number of contacts in household, coronavirus).

We identified 40 relevant published studies that report household secondary transmission. The estimated overall household SAR was 18.8% (95% confidence interval [CI] 15.4%-22.2%), which is higher than previously observed SARs for SARS-CoV and MERS-CoV. We observed that household SARs were significantly higher from symptomatic index cases than asymptomatic index cases, to adult contacts than children contacts, to spouses than other family contacts, and in households with one contact than households with three or more contacts.

To prevent the spread of SARS-CoV-2, people are being asked to stay at home worldwide. With suspected or confirmed infections referred to isolate at home, household transmission will continue to be a significant source of transmission.

To prevent the spread of SARS-CoV-2, people are being asked to stay at home worldwide. With suspected or confirmed infections referred to isolate at home, household transmission will continue to be a significant source of transmission.A key strategy to prevent a local outbreak during the COVID-19 pandemic is to restrict incoming travel. Once a region has successfully contained the disease, it becomes critical to decide when and how to reopen the borders. Here we explore the impact of border reopening for the example of Newfoundland and Labrador, a Canadian province that has enjoyed no new cases since late April, 2020. We combine a network epidemiology model with machine learning to infer parameters and predict the COVID-19 dynamics upon partial and total airport reopening, with perfect and imperfect quarantine conditions. Our study suggests that upon full reopening, every other day, a new COVID-19 case would enter the province. Under the current conditions, banning air travel from outside Canada is more efficient in managing the pandemic than fully reopening and quarantining 95% of the incoming population. Selleckchem AZD3514 Our study provides quantitative insights of the efficacy of travel restrictions and can inform political decision making in the controversy of reopening.Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays for antibody testing have been viewed as a cheap and rapidly deployable method for determining previous infection with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity. We report on nine lateral flow immunoassays currently available and compare their titer sensitivity in serum to a best-practice enzyme-linked immunosorbent assay (ELISA) and viral neutralization assay. For a small group of PCR-positive, we found two lateral flow immunoassay devices with titer sensitivity roughly equal to the ELISA; these devices were positive for all PCR-positive patients harboring SARS-CoV-2 neutralizing antibodies. One of these devices was deployed in Northern Italy to test its sensitivity and specificity in a real-world clinical setting. Using the device with fingerstick blood on a cohort of 27 hospitalized PCR-positive patients and seven hospitalized controls, ROC curve analysis gave AUC values of 0.7646 for IgG. For comparison, this assay was also tested with saliva from the same patient population and showed reduced discrimination between cases and controls with AUC values of 0.6841 for IgG. Furthermore, during viral neutralization testing, one patient was discovered to harbor autoantibodies to ACE2, with implications for how immune responses are profiled. We show here through a proof-of-concept study that these lateral flow devices can be as analytically sensitive as ELISAs and adopted into hospital protocols; however, additional improvements to these devices remain necessary before their clinical deployment.Background SARS-CoV-2 is a rapidly spreading coronavirus with a high incidence of severe upper respiratory infection that first presented in Wuhan, China in December 2019. Many factors have been identified as risk factors for SARS-CoV-2, with much attention being paid to body mass index (BMI), but little investigation has been done to investigate dysregulation of lipid profiles and diabetes, which are often comorbid in high BMI patients. Objective This study seeks to describe the impact of BMI, HDL, LDL, ApoA, ApoB, triglycerides, hemoglobin A1c (HbA1c), diabetes, alcohol and red wine intake on SARS-CoV-2 risk in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the risk of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through June 29, 2020. Logistic regression was performed on the target variables controlling for age, sex and ancestry. Results BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 risk (p less then 0.05) while HDL and ApoA were associated with decreased risk (p less then 0.001). Additionally, red wine intake was associated with reduced SARS-CoV-2 risk (p less then 0.05). LDL, ApoB and triglyceride levels were not found to be significantly associated with increased risk. Conclusion Elevated HDL and ApoA levels and alcohol intake, specifically red wine intake, were associated with reduced risk of testing positive for SARS-CoV-2, while type II diabetes and HbA1c were associated with increased risk. The effects of alcohol, type II diabetes and HbA1c levels may be indirect, mediated in part through regulation of HDL levels. In summary, our study corroborates the emerging picture that high HDL levels may confer protection against SARS-CoV-2.Cell surface receptor engagement is a critical aspect of viral infection. At low pH, binding of SARS-CoV and its ACE2 receptor has a tight interaction that catalyzes the fusion of the spike and endosomal membranes followed by genome release. Largely overlooked has been the role of neutral pH in the respiratory tract, where we find that SARS-CoV stabilizes a transition state that enhances the off-rate from its receptor. An alternative pH-switch is found in CoV-2-like coronaviruses of tropical pangolins, but with a reversed phenotype where the tight interaction with ACE2 is at neutral pH. We show that a single point mutation in pangolin-CoV, unique to CoV-2, that deletes the last His residue in their receptor binding domain perpetuates this tight interaction independent of pH. This tight bond, not present in previous respiratory syndromes, implies that CoV-2 stays bound to the highly expressed ACE2 receptors in the nasal cavity about 100 times longer than CoV. This finding supports the unfamiliar pathology of CoV-2, observed virus retention in upper respiratory tract 1 , longer incubation times and extended periods of shedding. Implications to combat pandemics that, like SARS-CoV-2, export evolutionarily successful strains via higher transmission rates due to retention in nasal epithelium and their evolutionary origin are discussed.The recent global pandemic caused by the new coronavirus SARS-CoV-2 presents an urgent need for new therapeutic candidates. While the importance of traditional in silico approaches such as QSAR in such efforts in unquestionable, these models fundamentally rely on structural similarity to infer biological activity and are thus prone to becoming trapped in the very nearby chemical spaces of already known ligands. For novel and unprecedented threats such as COVID-19 much faster and efficient paradigms must be devised to accelerate the identification of new chemical classes for rapid drug development. Here we report the development of a new biological activity-based modeling (BABM) approach that builds on the hypothesis that compounds with similar activity patterns tend to share similar targets or mechanisms of action. In BABM, compound activity profiles established on massive scale across multiple assays are used as signatures to predict compound activity in a new assay or against a new target. We first trained and validated this approach by identifying new antiviral lead candidates for Zika and Ebola based on data from ~0.5 million compounds screened against ~2,000 assays. BABM models were then applied to predict ~300 compounds not previously reported to have activity for SARS-CoV-2, which were then tested in a live virus assay with high (>30%) hit rates. The most potent compounds showed antiviral activities in the nanomolar range. These potent confirmed compounds have the potential to be further developed in novel chemical space into new anti-SARS-CoV-2 therapies. These results demonstrate unprecedented ability using BABM to predict novel structures as chemical leads significantly beyond traditional methods, and its application in rapid drug discovery response in a global public health crisis.The main protease (Mpro) of SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic, is a key antiviral drug target. While most SARS-CoV-2 Mpro inhibitors have a γ-lactam glutamine surrogate at the P1 position, we recently discovered several Mpro inhibitors have hydrophobic moieties at the P1 site, including calpain inhibitors II/XII, which are also active against human cathepsin L, a host-protease that is important for viral entry. To determine the binding mode of these calpain inhibitors and establish a structure-activity relationship, we solved X-ray crystal structures of Mpro in complex with calpain inhibitors II and XII, and three analogues of GC-376, one of the most potent Mpro inhibitors in vitro. The structure of Mpro with calpain inhibitor II confirmed the S1 pocket of Mpro can accommodate a hydrophobic methionine side chain, challenging the idea that a hydrophilic residue is necessary at this position. Interestingly, the structure of calpain inhibitor XII revealed an unexpected, inverted binding pose where the P1' pyridine inserts in the S1 pocket and the P1 norvaline is positioned in the S1' pocket.