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

Abstract

Aims: To investigate the association between long-term exposure to PM_2.5, PM_10, 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 PM_2.5 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 PM_2.5. PM_2.5 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.

Keywords: Air pollution; Breakthrough infection; COVID-19 vaccine; Immune response; Long-term exposure; Older adults.