BCG vaccination in health care providers and the protection against COVID-19

Abstract

A number of coronavirus disease 2019 (COVID-19) vaccine candidates have shown promising results, but substantial uncertainty remains regarding their effectiveness and global rollout. Boosting innate immunity with bacillus Calmette Guérin (BCG) or other live attenuated vaccines may also play a role in the fight against the COVID-19 pandemic. BCG has long been known for its nonspecific beneficial effects that are most likely explained by epigenetic and metabolic reprogramming of innate immune cells, termed trained immunity. In this issue of the JCI, Rivas et al. add to these arguments by showing that BCG-vaccinated health care providers from a Los Angeles health care organization had lower rates of COVID-19 diagnoses and seropositivity compared with unvaccinated individuals. Prospective clinical trials are thus warranted to explore the effects of BCG vaccination in COVID-19. We posit that beyond COVID-19, vaccines such as BCG that elicit trained immunity may mitigate the impact of emerging pathogens in future pandemics.

Figure 1. Model for trained immunity mechanisms that improve the antiviral host defense.

(A) Trained immunity is mediated by metabolic and epigenetic rewiring in the innate immune cells, leading to increased gene transcription and host defense against heterologous pathogens. (B) Following a first exposure to a live or live attenuated challenge, the innate immune response becomes poised via trained immunity to increase substantially following a second infection. (C) Trained immunity can be used as a tool for enhancing population immunity during a pandemic.