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

• DOI: 10.1084/jem.20220131
• Publication Date: 2022-06-16T13:59:26Z
• Authors: Qian Zhang; Daniela Matuozzo; Jérémie Le Pen; Danyel Lee; Leen Moens; Takaki Asano; Jonathan Bohlen; Zhiyong Liu; Marcela Moncada-V...; Yasemin Kendir-De...; Huie Jing; Lucy Bizien; Astrid Marchal; Hassan Abolhassani; Selket Delafontaine; Giorgia Bucciol; ; Laurent Abel; Hassan Abolhassani; Alessandro Aiuti; Ozge Metin Akcan; Saleh Al-Muhsen; Fahd Al-Mulla; Gulsum Alkan; Mark S. Anderson; Evangelos Andreakos; Andrés A. Arias; Jalila El Bakkouri; Hagit Baris Feldman; Alexandre Belot; Catherine M. Biggs; Dusan Bogunovic; Alexandre Bolze; Anastasiia Bondar...; Ahmed A. Bousfiha; Sefika Elmas Bozd...; Petter Brodin; Yenan Bryceson; Carlos D. Bustamante; Manish J. Butte; Giorgio Casari; John Christodoulou; Roger Colobran; Antonio Condino-Neto; Stefan N. Constan...; Megan A. Cooper; Clifton L. Dalgard; Murkesh Desai; Beth A. Drolet; Jamila El Baghdadi; Melike Emiroglu; Emine Hafize Erdeniz; Sara Espinosa-Pad...; Jacques Fellay; Carlos Flores; José Luis Franco; Antoine Froidure; Peter K. Gregersen; Bodo Grimbacher; Belgin Gulhan; Filomeen Haerynck; David Hagin; Rabih Halwani; Lennart Hammarström; James R. Heath; Sarah E. Henrickson; Elena W.Y. Hsieh; Eystein Husebye; Kohsuke Imai; Yuval Itan; Petr Jabandziev; Erich D. Jarvis; Timokratis Karami...; Adem Karbuz; Kai Kisand; Cheng-Lung Ku; Yu-Lung Lau; Yun Ling; Carrie L. Lucas; Tom Maniatis; Davood Mansouri; László Maródi; Ayse Metin; Isabelle Meyts; Joshua D. Milner; Kristina Mironska; Trine H. Mogensen; Tomohiro Morio; Lisa F.P. Ng; Luigi D. Notarangelo; Antonio Novelli; Giuseppe Novelli; Cliona O'Farrelly; Satoshi Okada; Keisuke Okamoto; Şadiye Kübra Tüte...; Tayfun Ozcelik; Qiang Pan-Hammars...; Maria Papadaki; Jean W. Pape; Aslinur Ozkaya Pa...; Rebeca Perez de D...; David S. Perlin; Graziano Pesole; Anna M. Planas; Petra Pokorna; Carolina Prando; Aurora Pujol; Lluis Quintana-Murci; Sathishkumar Rama...; Laurent Renia; Igor Resnick; Jacques G. Rivière; Carlos Rodríguez-...; Vanessa Sancho-Sh...; Anna Sediva; Mikko R.J. Seppänen; Mohammed Shahrooei; Anna Shcherbina; Katerina Slaba; Ondrej Slaby; Andrew L. Snow; Pere Soler-Palacín; Lien De Somer; András N. Spaan; Ivan Tancevski; Stuart G. Tangye; Ahmad Abou Tayoun; Dimitris Thanos; Stuart E. Turvey; K M Furkan Uddin; Mohammed J. Uddin; Diederik van de Beek; François Vermeulen; Donald C. Vinh; Horst von Bernuth; Joost Wauters; Carine Wouters; Aysun Yahsi; Saliha Kanik Yuksek; Mayana Zatz; Pawel Zawadzki; Helen C. Su; Jean-Laurent Casa...; Gulsum Ical Bayhan; Sevgi Keles; Ayca Kiykim; Selda Hancerli; Filomeen Haerynck; Benoit Florkin; Nevin Hatipoglu; Tayfun Ozcelik; Guillaume Morelle; Mayana Zatz; Lisa F.P. Ng; David Chien Lye; Barnaby Edward Young; Yee-Sin Leo; Clifton L. Dalgard; Richard P. Lifton; Laurent Renia; Isabelle Meyts; Emmanuelle Jouanguy; Lennart Hammarström; Qiang Pan-Hammars...; Bertrand Boisson; Paul Bastard; Helen C. Su; Stéphanie Boisson...; Laurent Abel; Charles M. Rice; Shen-Ying Zhang; Aurélie Cobat; Jean-Laurent Casa...
• Keywords: 360; Adult; 0301 basic medicine; Science::Medicine; SARS-CoV-2; SARS-Cov-2; Immunology; Brief Definitive Report; Inheritance Patterns; 610; COVID-19; Pneumonia; Settore MED/03 - GENETICA MEDICA; 618; Simplex-Virus Encephalitis; 03 medical and health sciences; Pyogenic Bacterial-Infections; Interferon Type I; Medicine and Health Sciences; Immunology and Allergy; Humans; :Medicine [Science]; Child

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk children, which is much lower than adults, remains unexplained. In an international cohort 112 children (<16 yr old) hospitalized for pneumonia, we report 12 (10.7%) aged 1.5–13 with (7 children), severe (3), and moderate (2) 4 the 15 known clinically recessive biochemically complete IFN immunity: X-linked TLR7 deficiency children) autosomal IFNAR1 (1), STAT2 TYK2 (3) deficiencies. Fibroblasts deficient IFNAR1, STAT2, are highly vulnerable to SARS-CoV-2. These deficiencies were not found 1,224 adults benign SARS-CoV-2 infection without (P = 1.2 × 10−11) overlapping age, sex, consanguinity, ethnicity characteristics. may ∼10% hospitalizations children.