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.
Original language | English |
---|---|
Article number | e20220131 |
Journal | Journal of Experimental Medicine |
Volume | 219 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Aug 2022 |
Keywords
- Adult
- COVID-19/genetics
- Child
- Humans
- Inheritance Patterns
- Interferon Type I
- Pneumonia
- SARS-CoV-2
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In: Journal of Experimental Medicine, Vol. 219, No. 8, e20220131, 01.08.2022.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
AU - COVID Human Genetic Effort
AU - Zhang, Qian
AU - Matuozzo, Daniela
AU - Le Pen, Jérémie
AU - Lee, Danyel
AU - Moens, Leen
AU - Asano, Takaki
AU - Bohlen, Jonathan
AU - Liu, Zhiyong
AU - Moncada-Velez, Marcela
AU - Kendir-Demirkol, Yasemin
AU - Jing, Huie
AU - Bizien, Lucy
AU - Marchal, Astrid
AU - Abolhassani, Hassan
AU - Delafontaine, Selket
AU - Bucciol, Giorgia
AU - Bayhan, Gulsum Ical
AU - Keles, Sevgi
AU - Kiykim, Ayca
AU - Hancerli, Selda
AU - Haerynck, Filomeen
AU - Florkin, Benoit
AU - Hatipoglu, Nevin
AU - Ozcelik, Tayfun
AU - Morelle, Guillaume
AU - Zatz, Mayana
AU - Ng, Lisa F P
AU - Lye, David Chien
AU - Young, Barnaby Edward
AU - Leo, Yee-Sin
AU - Dalgard, Clifton L
AU - Lifton, Richard P
AU - Renia, Laurent
AU - Meyts, Isabelle
AU - Jouanguy, Emmanuelle
AU - Hammarström, Lennart
AU - Pan-Hammarström, Qiang
AU - Boisson, Bertrand
AU - Bastard, Paul
AU - Su, Helen C
AU - Boisson-Dupuis, Stéphanie
AU - Abel, Laurent
AU - Rice, Charles M
AU - Zhang, Shen-Ying
AU - Cobat, Aurélie
AU - Casanova, Jean-Laurent
AU - van de Beek, Diederik
N1 - Funding Information: of Paris. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. J. Le Pen was supported by the Francois Wallace Monahan Postdoctoral Fellowship at The Rockefeller University and the European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). P. Bastard was supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). H.C. Su and H. Jing are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. G. Novelli and A. Novelli from the COVID Human Genetic Effort are supported by Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. I. Meyts is a Senior Clinical Investigator at the Research Foundation—Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, by the CSL-Behring Research Grant, by the KU Leuven C1 grant C16/18/007, by a VIB GC PID grant, by the FWO grants G0C8517N, G0B5120N, and G0E8420N and by the Jeffrey Modell Foundation. This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 948959). This work is supported by ERN-RITA. S. Delafontaine is supported by personal FWO grant 11F4421N. L. Renia and L.F.P. Ng were supported by the Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001; COVID19RF-0008; COVID19RF-060) and A*STAR COVID-19 research funding (H/20/04/g1/006). The Canarian Sequencing Hub is funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). Funding Information: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; the Rockefeller University; the St. Giles Foundation; the National Institutes of Health (NIH; R01AI088364 and R01AI63029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Award program (UL1 TR001866); a Fast Grant from Emergent Ventures; the Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics; the GSP Coordinating Center funded by the National Human Genome Research Institute (UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the JPB Foundation; the Meyer Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (EQU201903007798); the ANR GenMISC (ANR-21-COVR-039) ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics); the Square Foundation; Grandir—Fonds de solidarité pour l’enfance; Fonda-tion du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM); REACTing-INSERM; and the University Publisher Copyright: © 2022 Zhang et al.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
KW - Adult
KW - COVID-19/genetics
KW - Child
KW - Humans
KW - Inheritance Patterns
KW - Interferon Type I
KW - Pneumonia
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85136173099&partnerID=8YFLogxK
U2 - https://doi.org/10.1084/jem.20220131
DO - https://doi.org/10.1084/jem.20220131
M3 - Article
C2 - 35708626
SN - 0022-1007
VL - 219
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
M1 - e20220131
ER -