Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
Authors: Zhang Qian , Matuozzo Daniela , Le Pen Jérémie , Lee Danyel , Moens Leen , Asano Takaki , Bohlen Jonathan , Liu Zhiyong , Moncada-Velez Marcela , Kendir-Demirkol Yasemin , Jing Huie , Bizien Lucy , Marchal Astrid , Abolhassani Hassan , Delafontaine Selket , Bucciol Giorgia ,   COVID Human Genetic Effort, Abel Laurent , Abolhassani Hassan , Aiuti Alessandro , Akcan Ozge Metin , Al-Muhsen Saleh , Al-Mulla Fahd , Alkan Gulsum , Anderson Mark S. , Andreakos Evangelos , Arias Andrés A. , El Bakkouri Jalila , Baris Feldman Hagit , Belot Alexandre , Biggs Catherine M. , Bogunovic Dusan , Bolze Alexandre , Bondarenko Anastasiia , Bousfiha Ahmed A. , Bozdemir Sefika Elmas , Brodin Petter , Bryceson Yenan , Bustamante Carlos D. , Butte Manish J. , Casari Giorgio , Christodoulou John , Colobran Roger , Condino-Neto Antonio , Constantinescu Stefan N. , Cooper Megan A. , Dalgard Clifton L. , Desai Murkesh , Drolet Beth A. , El Baghdadi Jamila , Emiroglu Melike , Erdeniz Emine Hafize , Espinosa-Padilla Sara , Fellay Jacques , Flores Carlos , Franco José Luis , Froidure Antoine , Gregersen Peter K. , Grimbacher Bodo , Gulhan Belgin , Haerynck Filomeen , Hagin David , Halwani Rabih , Hammarström Lennart , Heath James R. , Henrickson Sarah E. , Hsieh Elena W.Y. , Husebye Eystein , Imai Kohsuke , Itan Yuval , Jabandziev Petr , Jarvis Erich D. , Karamitros Timokratis , Karbuz Adem , Kisand Kai , Ku Cheng-Lung , Lau Yu-Lung , Ling Yun , Lucas Carrie L. , Maniatis Tom , Mansouri Davood , Maródi László , Metin Ayse , Meyts Isabelle , Milner Joshua D. , Mironska Kristina , Mogensen Trine H. , Morio Tomohiro , Ng Lisa F.P. , Notarangelo Luigi D. , Novelli Antonio , Novelli Giuseppe , O'Farrelly Cliona , Okada Satoshi , Okamoto Keisuke , Tüter Öz Şadiye Kübra , Ozcelik Tayfun , Pan-Hammarström Qiang , Papadaki Maria , Pape Jean W. , Parlakay Aslinur Ozkaya , Perez de Diego Rebeca , Perlin David S. , Pesole Graziano , Planas Anna M. , Pokorna Petra , Prando Carolina , Pujol Aurora , Quintana-Murci Lluis , Ramaswamy Sathishkumar , Renia Laurent , Resnick Igor , Rivière Jacques G. , Rodríguez-Gallego Carlos , Sancho-Shimizu Vanessa , Sediva Anna , Seppänen Mikko R.J. , Shahrooei Mohammed , Shcherbina Anna , Slaba Katerina , Slaby Ondrej , Snow Andrew L. , Soler-Palacín Pere , De Somer Lien , Spaan András N. , Tancevski Ivan , Tangye Stuart G. , Abou Tayoun Ahmad , Thanos Dimitris , Turvey Stuart E. , Uddin K M Furkan , Uddin Mohammed J. , van de Beek Diederik , Vermeulen François , Vinh Donald C. , von Bernuth Horst , Wauters Joost , Wouters Carine , Yahsi Aysun , Kanik Yuksek Saliha , Zatz Mayana , Zawadzki Pawel , Su Helen C. , Casanova Jean-Laurent , Bayhan Gulsum Ical , Keles Sevgi , Kiykim Ayca , Hancerli Selda , Haerynck Filomeen , Florkin Benoit , Hatipoglu Nevin , Ozcelik Tayfun , Morelle Guillaume , Zatz Mayana , Ng Lisa F.P. , Lye David Chien , Young Barnaby Edward , Leo Yee-Sin , Dalgard Clifton L. , Lifton Richard P. , Renia Laurent , Meyts Isabelle , Jouanguy Emmanuelle , Hammarström Lennart , Pan-Hammarström Qiang , Boisson Bertrand , Bastard Paul , Su Helen C. , Boisson-Dupuis Stéphanie , Abel Laurent , Rice Charles M. , Zhang Shen-Ying , Cobat Aurélie , Casanova Jean-Laurent 
Published: June 2022

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 (&lt;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.