Clinical evidence on BCG vaccination and COVID-19 infection: A systematic review

The COVID-19 pandemic, starting in late 2019, led to the rapid development of SARS-CoV-2 vaccines, though early availability was limited, and variants like Delta and Omicron impacted their effectiveness. The Bacillus Calmette-Guérin (BCG) vaccine, used to prevent tuberculosis, has attracted interest for its potential non-specific protective effects against COVID-19. This review systematically evaluates the role of BCG vaccination in enhancing innate immune responses and its utility against COVID-19, focusing on mechanisms like trained immunity and cross-protection. It also discusses recent studies on BCG's impact on COVID-19 outcomes. Preliminary clinical trial findings suggest potential benefits of BCG vaccination against COVID-19, but the evidence remains inconclusive. Therefore, this review highlights the necessity of additional studies to determine whether BCG can prevent COVID-19 infection, mitigate severe outcomes and hospitalizations, and serve as a preventive tool for future viral pandemics.