Özçelik, TayfunZhang, QianMatuozzo, DanielaLe Pen, JérémieMoens, LeenAsano, TakakiBohlen, JonathanLiu, ZhiyongMoncada-Velez, MarcelaKendir-Demirkol, YaseminJing, HuieBizien, LucyMarchal, AstridAbolhassani, HassanDelafontaine, SelketBucciol, GiorgiaBayhan, Gulsum IcalKeles, SevgiKiykim, AycaHancerli, SeldaHaerynck, FilomeenFlorkin, BenoitHatipoğlu, NevinMorelle, GuillaumeZatz, MayanaNg, Lisa F. P.Lye, David ChienYoung, Barnaby EdwardLeo, Yee-SinDalgard, Clifton L.Lifton, Richard P.Renia, LaurentMeyts, IsabelleJouanguy, EmmanuelleHammarström, LennartPan-Hammarström, QiangBoisson, BertrandBastard, PaulSu, Helen C.Boisson-Dupuis, StéphanieAbel, LaurentaRice, Charles M.Zhang, Shen-YingCobat, AurélieCasanova, Jean-Laurent2023-02-272023-02-272022-08-01http://hdl.handle.net/11693/111853Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5–13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10−11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children. © 2022 Zhang et al.EnglishArticle10.1084/jem.202201310022-1007