Trained innate immunity and human adenovirus infection as a novel mechanism linked to the severe acute hepatitis of unknown origin in children during the COVID‐19 pandemic

Key points Recent clinical findings indicate that in severe acute hepatitis of unknown origin in children, the innate immune response underlies the main pathogenesis, regardless of the involved pathogens, including adenoviruses (AdVs) that predominantly affect the gut. The present work suggests that in the presence of trained immunity, the inflammation triggered by AdV infection is mild and confined to the gut, whereas without trained immunity, AdV infection can lead to viremia, severe inflammation, and even cytokine storms.