Bacille Calmette-Guérin (BCG) Vaccine and Potential Cross-Protection against SARS-CoV-2 Infection – Assumptions, Knowns, Unknowns and Need for Developing an Accurate Scientific Evidence Base

Nachega, Jean B.; Maeurer, Markus; Sam-Agudu, Nadia A.; Chakaya, Jeremiah; Katoto, Patrick D.M.; Zumla, Alimuddin

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4 + T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies.