Acute MIS-C is characterised by the impaired reactivation of SARS-CoV-2-reactive memory T cells, which is accompanied by the presence of TGFβ in T cells, B cells, and monocytes, along with the reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Here, TGFB1 is linked to COVID-19–associated multisystem inflammatory syndrome in children.