Association between long-term exposure to air pollutants with breakthrough SARS-CoV-2 infections and antibody responses among COVID-19 vaccinated older adults in Northern Italy

Aims: To investigate the association between long-term exposure to PM2.5 PM10 NO2 and O3 with SARS-CoV-2 breakthrough infections and COVID-19 vaccine-induced antibody responses in a northern Italian population-based sample of older adults. Methods: Within an ongoing prospective population-based study, we followed-up 1326 vaccinated individuals aged 65–83 years, with no prior SARS-CoV-2 infection, for their first positive SARS-CoV-2 swab until December 31st, 2022. We assessed spike IgG antibody levels in most participants (n = 1206). The 2019 annual mean levels of air pollutants derived from combined use of chemical-transport and random-Forest models (spatial resolution: 1Kmq) were individually assigned based on the latest residence address. We estimated multivariable-adjusted associations (per 1 interquartile range increase, IQR) of air pollutants with breakthrough infections using Cox models with time-dependent vaccine exposure; and with percent change in the IgG geometric mean using generalized additive models. Results: The mean (SD) age was 74.9 ± 4.1 years, and 50% were women. An IQR (1.2 μg/m3) increase in long-term PM2.5 exposure was associated with a 52% increase in breakthrough infection risk following a second vaccine and a 26% increase following a third vaccine. The effect vanished with the further increment of vaccination doses. Associations for NO2 were inconsistent. Ozone was negatively associated with breakthrough infection risk, but this association reversed in bi-pollutant models adjusting for PM2.5. PM2.5 was associated with a −7.3% (−13.9% to −0.2%) reduction in vaccine-induced IgG levels. The reduction became more pronounced as the time delay from vaccination increased, and with adjustment for NO2 co-exposure. Conclusion: In our population of vaccinated older adults, fine particulate matter exposure was independently associated with a higher risk of SARS-CoV-2 breakthrough infection and a lower antibody response, both effects being influenced by timely and repeated vaccination schedule.