Differential COVID-19-attributable mortality and BCG vaccine use in countries

Anita Shet; Debashree Ray; Neelika Malavige; Mathuram Santosham; Naor Bar-Zeev

Among vaccination strategies worldwide, Bacille Calmette Guérin (BCG) vaccine has the widest use and is accompanied by a strong safety profile. It is given in infancy for prevention of severe forms of tuberculosis. Epidemiological and randomized trial evidence suggest a protective effect of BCG on infant mortality via nonspecific heterologous protection against other infections 5 possibly through innate immune epigenetic mechanisms 6, 7 . BCG lowers experimental viremia in adult human volunteers through upregulation of interleukins such as IL-1β 8 . In a randomized placebo-controlled trial in Indonesia, BCG given monthly consecutively for 3 months significantly reduced incidence of acute upper respiratory infections among individuals aged >65years 9 . In a trial among Native Americans, BCG vaccination given during childhood showed efficacy in preventing tuberculosis up to 60 years after vaccination, indicating the durability of its protection 10 . Demonstration that exposure to BCG vaccination can ameliorate severe COVID-19 disease and lower mortality could rationalize a therapeutic or preventive strategy that can have immediately deployable global impact. Therefore, using existing publicly available data we examined at the ecological level whether country-level COVID-19 mortality was associated with BCG use in national immunization schedules.