NOD2-dependent BCG-induced trained immunity: A way to regulate innate responses to SARS-CoV2?

Bacillus Calmette-Guérin (BCG) vaccination was shown to reduce the susceptibility of respiratory viral infections by induction of potent innate immune memory termed trained immunity. Epidemiological studies on Covid-19 disease suggested that countries maintaining long-standing universal BCG vaccination policies have a lower number of SARS-CoV2 infections and reduced associated mortality. Large clinical trials are under way to confirm the benefits of BCG vaccinations on Covid-19. In this Perspective manuscript, we discuss possible immunological mechanisms of BCG-induced trained immunity in the context of SARS-CoV2 infection. Particularly, we hypothesize that NOD2 signaling activation by BCG in macrophages/monocytes could be determinant to tune innate immune responses against SARS-CoV2.