A Spatial and Contextual Exposome-Wide Association Study of COVID-19 Hospitalizations in Florida, United States

Abstract

Background and Aim: Recent studies suggested that long-term environmental exposures may be important determinants of COVID-19 severity. However, very few environmental factors have been studied, and often separately without considering the totality of the environment (i.e., the exposome). To address this gap, we conducted a spatial and contextual exposome-wide association study (ExWAS) of COVID-19 hospitalizations in Florida, United States (US). Methods: We obtained electronic health records data of 50,368 patients 18 years and older with a positive SARS-CoV-2 PCR/Antigen lab test or a COVID-19 diagnosis between March 2020 and October 2021 from the OneFlorida+ Data Trust. Patients’ exposures to 211 spatial and contextual exposome factors during 2015-2019 were integrated and spatiotemporally linked to their residential addresses. A two-phase analytical procedure was used. (1) A random 50:50 split divided the data into discovery and replication sets. Associations between COVID-19 hospitalizations and individual exposome factors were examined using mixed-effect logistic regression models, with multiple comparisons addressed. (2) A multivariable regression model including all variables that were statistically significant from both the discovery and replication sets was fitted. Odds ratio for each standard deviation increase (ORSD) and 95% confidence interval (95% CI) were reported. Results: A total of 12 and 21 variables were statistically significant in the discovery and replication sets, respectively. Among the 7 variables included in Phase 2, 3 variables remained statistically significant, including (1) hydrochloric acid (ORSD: 1.93, 95% CI: 1.11, 3.38), obtained from the US Environmental Protection Agency’s National Air Toxics Assessment, (2) density of fitness and recreational sports centers (ORSD: 0.94, 95% CI: 0.92, 0.97), assessed using the US Census Business Pattern, and (3) neighborhood deprivation index (ORSD: 1.09, 95% CI: 1.06, 1.12), derived using the American Community Survey. Conclusions: Long-term exposures to three spatial and contextual exposome factors were associated with COVID-19 hospitalizations in Florida, United States.