News & Comment

While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.

Considering immune responses through the framework of ‘integrated organ immunity’ could enable the design of a new class of universal vaccines.

In this Comment article, the authors alert us to recent studies of ancient DNA that advance our understanding of the origins of autoimmune disease, providing evidence that our disease risk has been shaped by pathogen-driven evolution.