Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Zhang Q, Matuozzo D, Le Pen J, Lee D, Moens L, Asano T, Bohlen J, Liu Z, Moncada-Velez M, Kendir-Demirkol Y, Jing H, Bizien L, Marchal A, Abolhassani H, Delafontaine S, Bucciol G, Bayhan GI, Keles S, Kiykim A, Hancerli S, Haerynck F, Florkin B, Hatipoglu N, Ozcelik T, Morelle G, Zatz M, Ng LFP, Lye DC, Young BE, Leo YS, Dalgard CL, Lifton RP, Renia L, Meyts I, Jouanguy E, Hammarström L, Pan-Hammarström Q, Boisson B, Bastard P, Su HC, Boisson-Dupuis S, Abel L, Rice CM, Zhang SY, Cobat A, Casanova JL, Abel L, Abolhassani H, Aiuti A, Akcan OM, Al-Muhsen S, Al-Mulla F, Alkan G, Anderson MS, Andreakos E, Arias AA, El Bakkouri J, Baris Feldman H, Belot A, Biggs CM, Bogunovic D, Bolze A, Bondarenko A, Bousfiha AA, Bozdemir SE, Brodin P, Bryceson Y, Bustamante CD, Butte MJ, Casari G, Christodoulou J, Colobran R, Condino-Neto A, Constantinescu SN, Cooper MA, Dalgard CL, Desai M, Drolet BA, El Baghdadi J, Emiroglu M, Erdeniz EH, Espinosa-Padilla S, Fellay J, Flores C, Franco JL, Froidure A, Gregersen PK, Grimbacher B, Gulhan B, Haerynck F, Hagin D, Halwani R, Hammarström L, Heath JR, Henrickson SE, Hsieh EWY, Husebye E, Imai K, Itan Y, Jabandziev P, Jarvis ED, Karamitros T, Karbuz A, Kisand K, Ku CL, Lau YL, Ling Y, Lucas CL, Maniatis T, Mansouri D, Maródi L, Metin A, Meyts I, Milner JD, Mironska K, Mogensen TH, Morio T, Ng LFP, Notarangelo LD, Novelli A, Novelli G, O'Farrelly C, Okada S, Okamoto K, Tüter Öz ŞK, Ozcelik T, Pan-Hammarström Q, Papadaki M, Pape JW, Parlakay AO, Perez de Diego R, Perlin DS, Pesole G, Planas AM, Pokorna P, Prando C, Pujol A, Quintana-Murci L, Ramaswamy S, Renia L, Resnick I, Rivière JG, Rodríguez-Gallego C, Sancho-Shimizu V, Sediva A, Seppänen MRJ, Shahrooei M, Shcherbina A, Slaba K, Slaby O, Snow AL, Soler-Palacín P, De Somer L, Spaan AN, Tancevski I, Tangye SG, Abou Tayoun A, Thanos D, Turvey SE, Uddin KMF, Uddin MJ, van de Beek D, Vermeulen F, Vinh DC, von Bernuth H, Wauters J, Wouters C, Yahsi A, Kanik Yuksek S, Zatz M, Zawadzki P, Su HC, Casanova JL.

Source :

J Exp Med

2022 Aug 1

Pmid / DOI:

PMID: 35708626

Abstract

Recessive 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.

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