Higher COVID-19 pneumonia risk associated with anti-IFN-? than with anti-IFN-? auto-Abs in children

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dc.contributor.authorBastard, Paul
dc.contributor.authorGervais, Adrian
dc.contributor.authorTaniguchi, Maki
dc.contributor.authorSaare, Liisa
dc.contributor.authorSarekannu, Karita
dc.contributor.authorLe Voyer, Tom
dc.contributor.authorPhilippot, Quentin
dc.date.accessioned2024-02-23T14:20:46Z
dc.date.available2024-02-23T14:20:46Z
dc.date.issued2024
dc.departmentNEÜen_US
dc.description.abstractWe found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2.en_US
dc.description.sponsorshipHoward Hughes Medical Institute; Rockefeller University; St. Giles Foundation; National Institutes of Health (NIH) [R01AI088364, R01AI163029, R21AI160576]; National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Award program [UL1TR001866]; Fisher Center for Alzheimer's Research Foundation; Meyer Foundation; JPB Foundation; Stavros Niarchos Foundation Institute for Global Infectious Disease Research; Agence Nationale de la Recherche (ANR) [ANR-10-IAHU-01, ANR-10-LABX-62-IBEID]; French Foundation for Medical Research (FRM) [EQU201903007798]; ANR GENVIR [ANR-20-CE93-003]; ANR AI2D [ANR-22-CE15-0046]; ANR AAILC [ANR-21-LIBA-0002]; European Union; Square Foundation, Grandir Fonds de solidarite pour l'enfance; Fondation du Souffle; SCOR Corporate Foundation for Science; French Ministry of Higher Education; Institut National de la Sante et de la Recherche Medicale (INSERM); University of Paris Cite; General Atlantic Foundation - European Research Council [HORIZON-HLTL-2021-ID: 101057100, KU Leuven C16/18/007]; FWO [G0B5120N (DADA2)]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; French Foundation for Medical Research [EA20170638020]; MD-PhD program of the Imagine Institute; (Fondation Bettencourt-Schueller); MEXT/JSPS KAKENHI [22H03041, 22KK0113]; AMED [JP21fk0108436, JP22fk0108514]; Instituto de Salud Carlos III (ISCIII) [FIS-PI21/01642]; Fonds de Recherche du Quebec -Sante, Senior Clinician-Scientist scholar award - Swedish Research Council; Knut and Alice Wallenberg Foundation - Estonian Research Council [PRG1117, PRG1428]; ISCIII [COV20_01333, COV20_01334, PI16/00759, PI18/00223, PI19/00208, PI20/00876, PI21/00211]; (FEDER) [IN607B 2020/08]; ACIS: BI-BACVIR; consorcio Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias [CB21/06/00103, IN845D 2020/23, IIN607A2021/05]; SpanishMinistry of Science and Innovation [RTC-2017-6471-1]; (AEI/FEDER, EU); Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias [FIISC19/43, PIFIISC22/27, OA18/017]; Fundacion MAPFRE Guanarteme [OA21/131]; Cabildo Insular de Tenerife [CGIEU0000219140]; (Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19) [ACCI20-759 CIBERER, TV3 COVID 2021-31-33, HORIZON-HLTH-2021-ID, 101057100]; Horizon 2020 program [824110, COVID-19/PID12342]; CERCA Program/Generalitat de Catalunya; Autoimmune Diseasesen_US
dc.description.sponsorshipThe 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, R01AI163029, and R21AI160576), the National Center for Advancing Translational Sciences, the NIH Clinical and Translational Science Award program (UL1TR001866), the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JPB Foundation, the Stavros Niarchos Foundation Institute for Global Infectious Disease Research, the program Investissement d'Avenir launched by the French Government and implemented by the Agence Nationale de la Recherche (ANR) (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 (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), ANR AI2D (ANR-22-CE15-0046), and ANR AAILC (ANR-21-LIBA-0002) projects, the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU COVIFERON Program (ANR-21-RHUS-08), the Square Foundation, Grandir Fonds de solidarite pour l'enfance, the 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, the University of Paris Cite and Imagine Institute, Battersea & Bowery Advisory Group, and William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director and Head of Business in EMEA, and the General Atlantic Foundation. I. Meyts is a senior clinical researcher at FWO Vlaanderen; I. Meyts is funded by the European Research Council under HORIZON-HLTL-2021-ID: 101057100 Undine, KU Leuven C16/18/007, and FWO grant G0B5120N (DADA2). L.D. Notarangelo and H.C. Su (members of the COVID Human Genetic Effort) were supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. P. Bastard was supported by the French Foundation for Medical Research (FRM, EA20170638020). P. Bastard and T. Le Voyerwere supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). P. Bastard was supported by the Poste CCA-INSERM-Bettencourt (with the support of the Fondation Bettencourt-Schueller). S. Okada was supported by MEXT/JSPS KAKENHI (grant numbers 22H03041 and 22KK0113) and AMED (grant numbers JP21fk0108436 and JP22fk0108514). L.I. Gonzalez-Granado is supported by the Instituto de Salud Carlos III (ISCIII) through the project FIS-PI21/01642 and cofunded by the European Union. D.C. Vinh is supported by a Fonds de Recherche du Quebec -Sante, Senior Clinician-Scientist scholar award. Q. Pan-Hammarstrom was funded by the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. K. Kisand's laboratory was funded by the Estonian Research Council grants PRG1117 and PRG1428. This study also received support from ISCIII (TRINEO: PI22/00162; DIAVIR: DTS19/00049; Resvi-Omics: PI19/01039 [A. Salas]; ReSVinext: PI16/01569 [F. Martinon-Torres]; Enterogen: PI19/01090 [F. Martinon-Torres]); OMI-COVI-VAC (PI22/00406 [F. Martinon-Torres] jointly financed by FEDER), GAIN: Grupos con Potencial de Crecimiento (IN607B 2020/08 [A.; Salas]); ACIS: BI-BACVIR (PRIS-3 [A. Salas]), and CovidPhy (SA 304 C [A. Salas]); and consorcio Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CB21/06/00103; F. Martinon-Torres); GEN-COVID (IN845D 2020/23, F. Martinon-Torres) and Grupos de Referencia Competitiva (IIN607A2021/05, F. Martinon-Torres). The study was funded by ISCIII (COV20_01333, COV20_01334, PI16/00759, PI18/00223, PI19/00208, PI20/00876, and PI21/00211), the SpanishMinistry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, EU), the Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias (FIISC19/43, PIFIISC22/27), Grupo DISA (OA18/017), Fundacion MAPFRE Guanarteme (OA21/131), Cabildo Insular de Tenerife (CGIEU0000219140 and Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19). A. Pujol is supported by ACCI20-759 CIBERER, H2020 Marato TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. This research is supported by the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases. Open Access funding provided by Rockefeller University.en_US
dc.identifier.doi10.1084/jem.20231353
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.issue2en_US
dc.identifier.pmid38175961en_US
dc.identifier.scopus2-s2.0-85181628485en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1084/jem.20231353
dc.identifier.urihttps://hdl.handle.net/20.500.12452/13303
dc.identifier.volume221en_US
dc.identifier.wosWOS:001136834800001en_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.titleHigher COVID-19 pneumonia risk associated with anti-IFN-? than with anti-IFN-? auto-Abs in childrenen_US
dc.typeArticleen_US

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