Effects of Long-Term Air Pollution Exposure on Disease Outcomes and Hybrid Immune Responses in SARS-CoV-2 Breakthrough Infections: A Study of the Yichang COVID-19 Antibody Longitudinal Survey (YC-CALS) in China.

Abstract

BACKGROUND As immunity wanes and viral mutations continue, the risk of endemic SARS-CoV-2 breakthrough infections (BTIs) remains. Air pollution is considered a risk factor for respiratory infection, but evidence of its association with SARS-CoV-2 BTIs is limited. OBJECTIVES We aimed to examine the effects of long-term exposure to air pollution on disease outcomes, immune responses, and antibody dynamics of SARS-CoV-2 BTIs. METHODS We gathered data on self-reported SARS-CoV-2 infections through questionnaires and measured IgG antibody levels using serological assays from a total of 6,875 participants from the Yichang COVID-19 Antibody Longitudinal Survey cohort in China. Air pollutant exposure (PM2.5, PM10, PM1, SO2, NO2, O3, and CO) was quantified using validated models for the past five years (2018 to 2022). Logistic and linear regression models were applied to analyze the associations between air pollutant levels and SARS-CoV-2 BTIs, Long COVID, COVID-19 hospitalization, and antibody responses. Quantile g-computation was used to assess the combined effects of pollutant mixtures. A linear mixed model was used to evaluate the effect of air pollution on antibody dynamics. RESULTS Per interquartile range (IQR) increase in PM2.5, SO2, NO2, and CO, the adjusted odds ratios (ORs) for SARS-CoV-2 BTIs were 1.65(95% CI: 1.30, 2.08), 1.30 (95% CI: 1.12, 1.50), 1.63 (95% CI: 1.20, 2.20), and 1.24 (95% CI: 1.06, 1.45). The ORs for PM2.5 were 1.78 (95% CI: 1.07, 3.02) and 2.02 (95% CI: 1.18, 3.54) for Long COVID and hospitalization. Per IQR increase in PM1 and NO2, IgG antibody percentages decreased by -2.31% (95% CI: -4.49%, -0.13%) and -2.69% (95% CI: -5.35%, -0.03%). Effects were stronger in older adults, those with comorbidities, and the under-vaccinated. The combined effect on SARS-CoV-2 BTIs was mainly driven by PM2.5 (59.4%), while the impact on IgG response was largely attributed to NO2 (63.7%). Exposure to the highest levels of PM2.5 (p = 0.002), PM1 (p < 0.001), and NO2 (p = 0.002) was associated with a faster IgG decline than the lowest. DISCUSSION Long-term exposure to air pollution increases the risk of SARS-CoV-2 BTIs and disease severity while weakening the immune response, particularly for vulnerable populations. https://doi.org/10.1289/EHP15660.