The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological evaluation using unsupervised machine learning

Abstract Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CSM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning to define the association between active BCG vaccination programs and CSM. Validation was performed using linear regression and country-specific modeling. CSM was lower for 80% of similarly clustered countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CSM increased significantly for each increase in the percent population over age 65. The total population of a country and BCG15 were significantly associated with improved CSM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CSM.