Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Danyel Lee, Jérémie Le Pen, Ahmad Yatim, Beihua Dong, Yann Aquino, Masato Ogishi, Rémi Pescarmona, Estelle Talouarn, Darawan Rinchai, Peng Zhang, Magali Perret, Zhiyong Liu, Iolanda Jordan, Sefika Elmas Bozdemir, Gulsum Iclal Bayhan, Camille Beaufils, Lucy Bizien, Aurelie Bisiaux, Weite Lei, Milena HasanJie Chen, Christina Gaughan, Abhishek Asthana, Valentina Libri, Joseph M. Luna, Fabrice Jaffré, H. Heinrich Hoffmann, Eleftherios Michailidis, Marion Moreews, Yoann Seeleuthner, Kaya Bilguvar, Shrikant Mane, Carlos Flores, Yu Zhang, Andrés A. Arias, Rasheed Bailey, Agatha Schlüter, Baptiste Milisavljevic, Benedetta Bigio, Tom Le Voyer, Marie Materna, Adrian Gervais, Marcela Moncada-Velez, Francesca Pala, Tomi Lazarov, Romain Levy, Anna Lena Neehus, Jérémie Rosain, Jessica Peel, João Farela Neves

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

Original languageEnglish
Article numbereabo3627
Issue number6632
Publication statusPublished - 10 Feb 2023


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