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The relationships between air pollution, genetic susceptibility, and COVID-19-related outcomes, as well as the potential interplays between air pollution and genetic susceptibility, remain largely unexplored. The Cox proportional hazards model was used to assess associations between long-term exposure to air pollutants and the risk of COVID-19 outcomes (infection, hospitalization, and death) in a COVID-19-naive cohort (n = 458,396). Additionally, associations between air pollutants and the risk of COVID-19 severity (hospitalization and death) were evaluated in a COVID-19 infection cohort (n = 110,216). Furthermore, this study investigated the role of host genetic susceptibility in the relationships between exposure to air pollutants and the development of COVID-19-related outcomes. Long-term exposure to air pollutants was significantly associated with an increased risk of COVID-19-related outcomes in the COVID-19 naive cohort. Similarly, in COVID-19 infection cohort, hazard ratios (HRs) for COVID-19 hospital admission were 1.23 (1.19, 1.27) for PM2.5 and 1.22 (1.17, 1.26) for PM10, whereas HRs for COVID-19 death were 1.28 (1.18, 1.39) for PM2.5 and 1.25 (1.16, 1.36) for PM10. Notably, significant interactions were found between PM2.5/PM10 and genetic susceptibility in COVID-19 death. In COVID-19 infection cohort, participants with both high genetic risk and high air pollutants exposure had 1.86- to 1.97-fold and 1.91- to 2.14-fold higher risk of COVID-19 hospitalization and death compared to those with both low genetic risk and low air pollutants exposure. Exposure to air pollution is significantly associated with an increased burden of severe COVID-19, and air pollution-gene interactions may play a crucial role in the development of COVID-19-related outcomes.

Original publication

DOI

10.1073/pnas.2421513122

Type

Journal

Proc natl acad sci u s a

Publication Date

11/03/2025

Volume

122

Keywords

COVID-19, air pollutants, cohort study, Humans, COVID-19, Air Pollution, Genetic Predisposition to Disease, Male, Female, Middle Aged, Cohort Studies, SARS-CoV-2, Air Pollutants, Hospitalization, Severity of Illness Index, Adult, Environmental Exposure, Aged, Particulate Matter, Proportional Hazards Models, Risk Factors