We detected 20 truncating heterozygous variants affecting 16 immune-related genes (CD84 [OMIM 604513], CD163 [OMIM 605545], IFI44 [OMIM 610468], IFI44L [OMIM 613975], IFIH1 [OMIM 606951], IFNA21 [OMIM 147584], IFNA4 [OMIM 147564], IFNA6 [OMIM 147566], IFNB1 [OMIM 147640], IL22RA2 [OMIM 606648], IRAK3 [OMIM 604459], LY9 [OMIM 600684], NLRP12 [OMIM 609648], NLRP2 [OMIM 609364], RAB27A [OMIM 603868], and TLR6 [OMIM 605403]) in 14 patients with MIS-C (Table). This evidence concerns the gene IFNA4 and COVID-19–associated multisystem inflammatory syndrome in children.