ABSTRACT
Human monoclonal antibodies from convalescent individuals that target the SARS-CoV-2 spike protein have been deployed as therapeutics against SARS-CoV-2. However, nearly all of these antibodies have been rendered obsolete by SARS-CoV-2 variants that evolved to resist similar, naturally occurring antibodies. Here, we describe the development of human monoclonal antibodies that bind the ACE2 receptor rather than the viral spike protein. These antibodies block infection by all ACE2 binding sarbecoviruses, including emergent SARS-CoV-2 variants. Structural and biochemical analyses revealed that the antibodies target an ACE2 epitope that engages SARS-CoV-2 spike. Importantly, the antibodies do not inhibit ACE2 enzymatic activity, nor do they induce ACE depletion from cell surfaces. The antibodies exhibit favorable pharmacology and protect human ACE2 knock-in mice against SARS-CoV-2 infection. Such antibodies should be useful prophylactic and treatment agents against any current and future SARS-CoV-2 variants, as well as ACE2-binding sarbecoviruses that might emerge as future pandemic threats.
ABSTRACT
BackgroundThe EPICOVID19-RS study conducted 10 population-based surveys in Rio Grande do Sul (Southern Brazil), starting early in the epidemic. The sensitivity of the rapid point-of-care test used in the first eight surveys has been shown to decrease over time after some phases of the study were concluded. The 9th survey used both the rapid test and an enzyme-linked immunosorbent assay (ELISA) test, which has a higher and stable sensitivity. MethodsWe provide a theoretical justification for a correction procedure of the rapid test estimates, assess its performance in a simulated dataset and apply it to empirical data from the EPICOVID19-RS study. COVID-19 deaths from official statistics were used as an indicator of the temporal distribution of the epidemic, under the assumption that fatality is constant over time. Both the indicator and results from the 9th survey were used to calibrate the temporal decay function of the rapid tests sensitivity from a previous validation study, which was used to estimate the true sensitivity in each survey and adjust the rapid test estimates accordingly. ResultsSimulations corroborated the procedure is valid. Corrected seroprevalence estimates were substantially larger than uncorrected estimates, which were substantially smaller than respective estimates from confirmed cases and therefore clearly underestimate the true infection prevalence. ConclusionCorrecting biased estimates requires a combination of data and modelling assumptions. This work illustrates the practical utility of analytical procedures, but also the critical need for good quality, populationally-representative data for tracking the progress of the epidemic and substantiate both projection models and policy making.
ABSTRACT
Population based data on COVID-19 are essential for guiding public policies. We report on the first of a series of planned seroprevalence surveys relying upon on household probabilistic samples of 133 large sentinel cities in Brazil, including 25,025 participants from all 26 states and the Federal District. Seroprevalence of antibodies to SARS-CoV-2, assessed using a lateral flow rapid test, varied markedly across the countrys cities and regions, from below 1% in most cities in the South and Center-West regions to up to 25% in the city of Breves in the Amazon (North) region. Eleven of the 15 cities with the highest seroprevalence were located in the North, including the six cities with highest prevalence which were located along a 2,000 km stretch of the Amazon river. Overall seroprevalence for the 90 cities with sample size of 200 or greater was 1.4% (95% CI 1.3-1.6). Extrapolating this figure to the population of these cities, which represent 25% of the countrys population, led to an estimate of 760,000 cases, as compared to the 104,782 cases reported in official statistics. Seroprevalence did not vary significantly between infancy and age 79 years, but fell by approximately two-thirds after age 80 years. Prevalence was highest among indigenous people (3.7%) and lowest among whites (0.6%), a difference which was maintained when analyses were restricted to the North region, where most indigenous people live. Our results suggest that pandemic is highly heterogenous, with rapid escalation in Brazils North and Northeast, and slow progression in the South and Center-West regions.
