Abstract

Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection = 56.06; 93.4% male; 82.7% European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category; 306 (31.1%) reported at least one post-acute COVID-19 symptom at 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. The asthma PRS was associated with severe COVID-19 category (odds ratio [OR] = 1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β = .09, p = .01), independently of respiratory disease diagnosis. Severe COVID-19 category was also associated with the allergic disease PRS (OR = 1.97, [1.26-3.07]) and the PRS for COVID-19 hospitalization (OR = 1.35, [1.01-1.82]). PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. Recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population.

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