Modulation of COVID-19 incidence by environmental stressors is variant between pre-Omicron and Omicron periods

COVID-19 had a devastating impact on humanity. We investigated how residential air pollution (ozone (O 3 ), nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 )) and meteorological factors (temperature (Temp), precipitation (Prec)) are associated with COVID-19 incidence in Baden-Württemberg (BW), Germany. We utilized data from the Copernicus Atmosphere Monitoring Service and the Copernicus Climate Change Service to model environmental exposure from 2020 to 2022 in postal code areas in BW. Health insurance data on SARS-CoV-2 infections were provided from the health insurance AOK BW on a quarterly level covering approximately 12 million person-years. We examined the spatiotemporal variability with a generalized additive model including various stressors, demographic factors, and area-wide data, offering a comprehensive analysis of the environmental stressor- COVI-10 incidence associations. In 2022, during the prevalence of the Omicron variant, the number of COVID-19 cases tripled compared to 2020. During the pre-Omicron period, COVID-19 incidence showed a positive association with PM 2.5 (relative risk [RR] 2.41; 95% confidence interval [CI] (2.31, 2.52)), a negative association with Temp (RR 0.39 (0.32, 0.48)), and no clear or slight associations with O 3 , Prec, and NO 2 . During the Omicron period, there were either no clear or slight negative associations with Temp (RR 0.92 (0.74, 1.30)), PM 2·5 (RR 0.70 (0.64, 0.79)), NO 2 , and Prec and a negative association with O 3 (RR 0.46 (0.40, 0.53)). The analysis found clear links between environmental stressors and COVID-19 incidence, which strongly differed between pre-Omicron and Omicron periods. Consideration of environmental stressor concentration could be relevant in the management of the pandemic.