Authors identified the presence of autosomal recessive deficiencies of OAS1, OAS2, or RNASEL (OAS1 p.R47*, OAS2 p.R535Q, p.Q258L, and p.V290I, and RNASEL p.G59S + E265*) as genetic etiologies of MIS-C in 5 unrelated children. Here, OAS2 is linked to COVID-19–associated multisystem inflammatory syndrome in children.