RESUMO
Community-level seroprevalence surveys are needed to determine the proportion of the population with previous SARS-CoV-2 infection, a necessary component of COVID-19 disease surveillance. In May, 2020, we conducted a cross-sectional seroprevalence study of IgG antibodies for nucleocapsid of SARS-CoV-2 among the residents of Blaine County, Idaho, a ski resort community with high COVID-19 attack rates in late March and Early April (2.9% for ages 18 and older). Participants were selected from volunteers who registered via a secure web link, using prestratification weighting to the population distribution by age and gender within each ZIP Code. Participants completed a survey reporting their demographics and symptoms; 88% of volunteers who were invited to participate completed data collection survey and had 10 ml of blood drawn. Serology was completed via the Abbott Architect SARS-CoV-2 IgG immunoassay. Primary analyses estimated seroprevalence and 95% credible intervals (CI) using a hierarchical Bayesian framework to account for diagnostic uncertainty. Stratified models were run by age, sex, ZIP Code, ethnicity, employment status, and a priori participant-reported COVID-19 status. Sensitivity analyses to estimate seroprevalence included base models with post-stratification for ethnicity, age, and sex, with or without adjustment for multi-participant households. IgG antibodies to the virus that causes COVID-19 were found among 22.7% (95% CI: 20.1%, 25.5%) of residents of Blaine County. Higher levels of antibodies were found among residents of the City of Ketchum 34.8% (95% CI 29.3%, 40.5%), compared to Hailey 16.8% (95%CI 13.7%, 20.3%) and Sun Valley 19.4% (95% 11.8%, 28.4%). People who self-identified as not believing they had COVID-19 had the lowest prevalence 4.8% (95% CI 2.3%, 8.2%). The range of seroprevalence after correction for potential selection bias was 21.9% to 24.2%. This study suggests more than 80% of SARS-CoV-2 infections were not reported. Although Blaine County had high levels of SARS-CoV-2 infection, the community is not yet near the herd immunity threshold.
RESUMO
CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5+ T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5+ T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.