Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 219, Issue 8, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220131
Keywords
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Categories
Funding
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364, R01AI63029]
- National Center for Advancing Translational Sciences
- NIH Clinical and Translational Science Award program [UL1 TR001866]
- Emergent Ventures
- Mercatus Center at George Mason University
- Yale Center for Mendelian Genomics
- National Human Genome Research Institute [UM1HG006504, U24HG008956]
- Yale High Performance Computing Center [S10OD018521]
- Fisher Center for Alzheimer's Research Foundation
- JPB Foundation
- Meyer Foundation
- French National Research Agency (ANR) [ANR-10-IAHU-01]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- French Foundation for Medical Research [EQU201903007798]
- ANR GenMISC [ANR-21-COVR-039]
- ANRS-COV05
- ANR GENVIR [ANR-20-CE93-003]
- ANR AABIFNCOV [ANR-20-CO11-0001]
- European Union [824110]
- Square Foundation
- Grandir-Fonds de solidarite pour l'enfance
- Fondation du Souffle
- SCOR Corporate Foundation for Science
- French Ministry of Higher Education, Research, and Innovation
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- REACTing-INSERM
- University of Paris
- NIH [P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, R01AI161444]
- George Mason University
- G. Harold and Leila Y. Mathers Charitable Foundation
- Bawd Foundation
- Francois Wallace Monahan Postdoctoral Fellowship at The Rockefeller University
- European Molecular Biology Organization Long-Term Fellowship [ALTF 380-2018]
- MD-PhD program of the Imagine Institute
- Fondation Bettencourt Schueller
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH
- Regione Lazio [A0375-2020-36663]
- CSL Behring Chair of Primary Immunodeficiencies
- CSL-Behring Research Grant
- KU Leuven C1 [C16/18/007]
- VIB GC PID grant
- FWO [G0C8517N, G0B5120N, G0E8420N, 11F4421N]
- Jeffrey Modell Foundation
- European Research Council [948959]
- ERN-RITA
- Singapore National Medical Research Council [COVID19RF-001, COVID19RF-0008, COVID19RF-060]
- A*STAR COVID-19 research funding [H/20/04/g1/006]
- Instituto de Salud Carlos III [COV20_01333, COV20_01334]
- Spanish Ministry of Science and Innovation [RTC-2017-6471-1]
- Cabildo Insular de Tenerife [CGIEU0000219140]
- personal FWO [11F4421N]
- European Research Council (ERC) [948959] Funding Source: European Research Council (ERC)
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In an international cohort of 112 hospitalized children with COVID-19 pneumonia, 12 children with recessive inborn errors of type I interferon immunity were identified. These deficiencies may contribute to the development of COVID-19 pneumonia in children. Additionally, these deficiencies were not found in individuals without pneumonia from SARS-CoV-2 infection.
In an international cohort of 112 children hospitalized for moderate to critical COVID-19 pneumonia, we identified 12 children with one of four known recessive inborn errors of type I interferon immunity: X-linked TLR7 and autosomal IFNAR1, STAT2, and TYK2 deficiencies. 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 x 10(-11)) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie similar to 10% of hospitalizations for COVID-19 pneumonia in children.
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