Comorbidities associated with regional variations in COVID-19 mortality revealed by population-level analysis

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), has developed into a global health crisis. Understanding the risk factors for poor outcomes of COVID-19 is thus important for successful management and control of the pandemic. However, the progress and severity of the epidemic across different regions show great differentiations. We hypothesized the origination of these differences are based on location-dependent variations in underlying population-wide health factors. Disease prevalence or incidence data of states and counties of the United States were collected for a group of chronic diseases, including hypertension, diabetes, obesity, stroke, coronary heart disease, heart failure, physical inactivation, and common cancers (e.g., lung, colorectal, stomach, kidney and renal). Correlation and regression analysis identified the prevalence of heart failure as a significant positive factor for region-level COVID-19 mortality. Similarly, the incidence of gastric cancer and thyroid cancer were also identified as significant factors contributing to regional variation in COVID-19 mortality. To explore the implications of these results, we re-analyzed the RNA-seq data for stomach adenocarcinoma (STAD) and colon carcinoma (COAD) from The Cancer Genome Atlas (TCGA) project. We found that expression of genes in the immune response pathways were more severely disturbed in STAD than in COAD, implicating higher probability for STAD patients or individuals with precancerous chronic stomach diseases to develop cytokine storm once infected with COVID-19. Taken together, we conclude that location variations in particular chronic diseases and cancers contribute significantly to the regional variations in COVID-19 mortality.