LAUSR

Description Multisystem inflammatory syndrome in children is caused by abnormal cell activation The clearest determinant of COVID-19 severity is age, with the majority of children experiencing mild or asymptomatic infections (1). But one disease presentation observed during the peak of the pandemic shows an opposite pattern. The rare but sometimes life-threatening multisystem inflammatory syndrome in children (MIS-C) has been a major cause of pediatric morbidity and mortality during the pandemic. Symptoms of MIS-C overlap partially with Kawasaki disease, a postinfectious vasculitis, and with toxic shock syndrome, a bacterial toxin–mediated disease caused by nonspecific activation of T lymphocytes by so-called superantigens. On page 554 of this issue, Lee et al. (2) report that variants in genes encoding the 2′-5′-oligoadenylate synthetase (OAS)–ribonuclease L (RNase L) viral RNA sensing pathway lead to exuberant inflammatory responses in myeloid cells in individuals with MIS-C. But why does MIS-C develop 1 month after the initial infection?