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Long-term exposure to air pollution and COVID-19 mortality and morbidity in Denmark: Who is most susceptible? (AIRCODEN)

Principal Investigator: 

University of Copenhagen, Denmark

This study will investigate whether exposure to air pollution increases the risk of severe COVID-19 outcomes, and identify the most susceptible groups by socioeconomic status, ethnicity, and comorbidities. Between March and December 2020, the investigators followed more than 3 million adults in Denmark. They will evaluate whether long- (40 years) and short- (1 year) term exposure to several common air pollutants increased the risk of COVID-19 hospitalization and mortality.

Funded under

Background: One of the important public health objectives in the midst of COVID-19 epidemic, is to identify key modifiable factors that could worsen the severity of the health outcomes among individuals with COVID-19. Long-term exposure to air pollution increases the risk of respiratory and cardiometabolic diseases, which in turn increases the risk of death from COVID-19, leading to the hypothesis that air pollution may increase susceptibility to mortality and morbidity from COVID-19. Early (non-peer-reviewed) results from a nationwide study in the US showed that even a small increase of 1 μg/m3 in long-term exposure to particulate matter < 2.5 μm (PM2.5) led to a large increase in the COVID-19 death rate of 8%, but were criticized for possibly grossly overestimating the effect of air pollution, for several reasons. The major weakness of the US study is its ecological design, where mortality rates in 3,080 USA counties were compared to crude, county-average 17-year mean PM2.5 levels, with lack of individual level data on exposure, outcome, and important confounders (e.g., socio-economic status (SES), lifestyle, and co-morbidities). It has been shown that the associations between long-term PM2.5 exposure and overall mortality in the US are substantially weaker in comparison with those observed in Denmark (7% vs. 26% increase per 10 μg/m3 in PM2.5), implicating possibly even stronger susceptibility of COVID-19 patients to air pollution in Denmark than in the US. The internationally unique Danish research infrastructure, with access to individual-level data on air pollution exposure, COVID-19 deaths and hospitalization, and relevant confounders and effect modifiers, provides a framework that can directly address the limitations of the early ecological approaches and provide a state-of-the-art study on long-term exposure to air pollution and COVID-19 mortality and morbidity.

Aim: To investigate whether long-term exposure to air pollution increases the risk of COVID-19 related mortality and hospitalizations, and to identify the most susceptible groups by SES, ethnicity and comorbidities.

Methods: A cohort of 3,056,854 Danes age 40 years or older on March 1st, 2020, will be followed until the date of COVID-19 related death (hospitalization), death from other reasons, emigration, or the end of follow-up on 31.12.2020. We will estimate the association between long-term exposure to air pollution (40-year (1979-2019) and 1-year (2019) residential mean levels of PM2.5, particulate matter < 10 μm in diameter (PM10), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3) and COVID-19 mortality and hospitalizations, using Cox regression models, adjusting for individual-level (education, income, employment status, housing, marital status, and country of origin) and area-level (parish) SES factors (population density, mean income, % unemployment, % primary or lower education, access to healthcare). Effect modification by individual-level SES, ethnicity and co-morbidities with cardiovascular disease, respiratory diseases, diabetes, lung cancer and dementia, and ethnicity will be evaluated by entering interaction terms into the model.