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

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dc.contributor.authorZhang, Qian
dc.contributor.authorMatuozzo, Daniela
dc.contributor.authorLe Pen, Jeremie
dc.contributor.authorLee, Danyel
dc.contributor.authorMoens, Leen
dc.contributor.authorAsano, Takaki
dc.contributor.authorBohlen, Jonathan
dc.date.accessioned2024-02-23T14:20:46Z
dc.date.available2024-02-23T14:20:46Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractIn 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.en_US
dc.description.sponsorshipHoward 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)en_US
dc.description.sponsorshipWe thank the patients' families for agreeing to participate in our research.; 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 solidarite pour l'enfance; Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19); Institut National de la Sante et de la Recherche Medicale (INSERM); REACTing-INSERM; and the University 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 cientificas del ITER para colaborar en la lucha contra la COVID-19).en_US
dc.identifier.doi10.1084/jem.20220131
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.issue8en_US
dc.identifier.pmid35708626en_US
dc.identifier.scopus2-s2.0-85136173099en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1084/jem.20220131
dc.identifier.urihttps://hdl.handle.net/20.500.12452/13301
dc.identifier.volume219en_US
dc.identifier.wosWOS:000866223500001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherRockefeller Univ Pressen_US
dc.relation.ispartofJournal Of Experimental Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[Keyword Not Available]en_US
dc.titleRecessive inborn errors of type I IFN immunity in children with COVID-19 pneumoniaen_US
dc.typeArticleen_US

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