Abstract
(1) Background: In the absence of individual level information, the aim of this study was to identify the regional key features explaining SARS-CoV-2 infections and COVID-19 deaths during the upswing of the second wave in Germany. (2) Methods: We used COVID-19 diagnoses and deaths from 1 October to 15 December 2020, on the county-level, differentiating five two-week time periods. For each period, we calculated the age-standardized COVID-19 incidence and death rates on the county level. We trained gradient boosting models to predict the incidence and death rates by 155 indicators and identified the top 20 associations using Shap values. (3) Results: Counties with low socioeconomic status (SES) had higher infection and death rates, as had those with high international migration, a high proportion of foreigners, and a large nursing home population. The importance of these characteristics changed over time. During the period of intense exponential increase in infections, the proportion of the population that voted for the Alternative for Germany (AfD) party in the last federal election was among the top characteristics correlated with high incidence and death rates. (4) Machine learning approaches can reveal regional characteristics that are associated with high rates of infection and mortality.