Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19.

Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections as well as of reported transcriptomic alterations in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that mimic viral infections by, consistent with the present concept of trained immunity, upregulation of antiviral defense response, and oppose viral infections by, inconsistent with the concept, downregulation of myeloid cell activation. These durability and mechanistic insights argue against possible indiscriminate use of the vaccine and activated innate immune response associated safety concerns in COVID-19, in that order.