Long-Term Exposure to Ambient Air Pollution and Mortality among Four Million COVID-19 Cases in Italy: The EpiCovAir Study

BACKGROUND: The role of chronic exposure to ambient air pollutants in increasing COVID-19 fatality is still unclear. OBJECTIVES: The study aimed to investigate the association between long-term exposure to air pollutants and mortality among 4 million COVID-19 cases in Italy. METHODS: We obtained individual records of all COVID-19 cases identified in Italy from February 2020 to June 2021. We assigned 2016–2019 mean concentrations of particulate matter (PM) with aerodynamic diameter [Formula: see text] ([Formula: see text]), PM with aerodynamic diameter [Formula: see text] ([Formula: see text]), and nitrogen dioxide ([Formula: see text]) to each municipality ([Formula: see text]) as estimates of chronic exposures. We applied a principal component analysis (PCA) and a generalized propensity score (GPS) approach to an extensive list of area-level covariates to account for major determinants of the spatial distribution of COVID-19 case–fatality rates. Then, we applied generalized negative binomial models matched on GPS, age, sex, province, and month. As additional analyses, we fit separate models by pandemic periods, age, and sex; we quantified the numbers of COVID-19 deaths attributable to exceedances in annual air pollutant concentrations above predefined thresholds; and we explored associations between air pollution and alternative outcomes of COVID-19 severity, namely hospitalizations or accesses to intensive care units. RESULTS: We analyzed 3,995,202 COVID-19 cases, which generated 124,346 deaths. Overall, case–fatality rates increased by 0.7% [95% confidence interval (CI): 0.5%, 0.9%], 0.3% (95% CI: 0.2%, 0.5%), and 0.6% (95% CI: 0.5%, 0.8%) per [Formula: see text] increment in [Formula: see text] , [Formula: see text] , and [Formula: see text] , respectively. Associations were higher among elderly subjects and during the first (February 2020–June 2020) and the third (December 2020–June 2021) pandemic waves. We estimated [Formula: see text] COVID-19 deaths were attributable to pollutant levels above the World Health Organization 2021 air quality guidelines. DISCUSSION: We found suggestive evidence of an association between long-term exposure to ambient air pollutants with mortality among 4 million COVID-19 cases in Italy. https://doi.org/10.1289/EHP11882