Epidemiologic and animal studies both support relationships between exposures to per- and polyfluoroalkyl substances (PFAS) and harmful effects on the immune system. Accordingly, PFAS have been identified as potential environmental risk factors for adverse COVID-19 outcomes. Here, we examine associations between PFAS contamination of U.S. community water systems (CWS) and county-level COVID-19 mortality records. Our analyses leverage two datasets: one at the subnational scale (5371 CWS serving 621 counties) and one at the national scale (4798 CWS serving 1677 counties). The subnational monitoring dataset was obtained from statewide drinking monitoring of PFAS (2016-2020) and the national monitoring dataset was obtained from a survey of unregulated contaminants (2013-2015). We conducted parallel analyses using multilevel quasi-Poisson regressions to estimate cumulative incidence ratios for the association between county-level measures of PFAS drinking water contamination and COVID-19 mortality prior to vaccination onset (Jan-Dec 2020). In the primary analyses, these regressions were adjusted for several county-level sociodemographic factors, days after the first reported case in the county, and total hospital beds. In the subnational analysis, detection of at least one PFAS over 5 ng/L was associated with 12% higher [95% CI: 4%, 19%] COVID-19 mortality. In the national analysis, detection of at least one PFAS above the reporting limits (20-90 ng/L) was associated with 13% higher [95% CI: 8%, 19%] COVID-19 mortality. Our findings provide evidence for an association between area-level drinking water PFAS contamination and higher COVID-19 mortality in the United States. These findings reinforce the importance of ongoing state and federal monitoring efforts supporting the U.S. Environmental Protection Agency's 2024 drinking water regulations for PFAS. More broadly, this example suggests that drinking water quality could play a role in infectious disease severity. Future research would benefit from study designs that combine area-level exposure measures with individual-level outcome data.
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