Interactive effects of long-Term exposure to air pollutants on SARS-CoV-2 infection and severity: A northern Italian population-based cohort study

Background We examined interactions, to our knowledge not yet explored, between long-Term exposures to particulate matter (PM10) with nitrogen dioxide (NO2) and ozone (O3) on SARS-CoV-2 infectivity and severity. Methods We followed 709,864 adult residents of Varese Province from 1 February 2020 until the first positive test, COVID-19 hospitalization, or death, up to 31 December 2020. We estimated residential annual means of PM10, NO2and O3in 2019 from chemical-Transport and random-forest models. We estimated interactive effects of pollutants with urbanicity on SARS-CoV-2 infectivity, hospitalization, and mortality endpoints using Cox regression models adjusted for socio-demographic factors and comorbidities, and additional cases due to interactions using Poisson models. Results 41,065 individuals were infected, 5,203 were hospitalized and 1,543 died from COVID-19 during follow-up. Mean PM10was 1.6 times higher and NO22.6 times higher than WHO limits, with wide gradients between urban and non-urban areas. PM10and NO2were positively associated with SARS-CoV-2 infectivity and mortality, and PM10with hospitalizations in urban areas. Interaction analyses estimated that the effect of PM10(per 3.5 µg/m3) on infectivity was strongest in urban areas (HR=1.12, 95%CI:1.09-1.16), corresponding to 854 additional cases per 100,000 person-years, and in areas at high NO2co-exposure (HR=1.15, 1.08-1.22). At higher levels of PM10co-exposure the protective association of ozone reversed (HR=1.32, 1.17-1.49), yielding to 278 additional cases per µg/m3increase in O3. We estimated similar interactive effects for severity endpoints. Conclusions We estimate that interactive effects between pollutants exacerbated the burden of SARS-CoV-2 pandemic in urban areas.