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

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Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Title:
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Journal Title:
Journal of Experimental Medicine
Authors:
Paul Bastard, Adrian Gervais, Maki Taniguchi, Liisa Saare, Karita Särekannu, Tom Le Voyer, Quentin Philippot, Jérémie Rosain, Lucy Bizien, Takaki Asano, Marina Garcia-Prat, Alba Parra-Martínez, Mélanie Migaud, Miyuki Tsumura, Francesca Conti, Alexandre Belot, Jacques G. Rivière, Tomohiro Morio, Junko Tanaka, Etienne Javouhey, Filomeen Haerynck, Sotirija Duvlis, Tayfun Ozcelik, Sevgi Keles, Yacine Tandjaoui-Lambiotte, Simon Escoda, Maya Husain, Qiang Pan-Hammarström, Lennart Hammarström, Gloria Ahlijah, Anthony Abi Haidar, Camille Soudee, Vincent Arseguel, Hassan Abolhassani, Sabina Sahanic, Ivan Tancevski, Yoko Nukui, Seiichi Hayakawa, George P. Chrousos, Athanasios Michos, Elizabeth-Barbara Tatsi, Filippos Filippatos, Agusti Rodriguez-Palmero, Jesus Troya, Imran Tipu, Isabelle Meyts, Lucie Roussel, Sisse Rye Ostrowski, Laire Schidlowski, Carolina Prando, Antonio Condino-Neto, Nathalie Cheikh, Ahmed A. Bousfiha, Jalila El Bakkouri, , Sergio Aguilera-Albesa, Suzan A. AlKhater, Gulsum Alkan, Riccardo Castagnoli, Cyril Cyrus, Sefika Elmas Bozdemir, Melike Emiroglu, Belgin Gulhan, Emine Hafize Erdeniz, Nevin Hatipoglu, Gülsün Iclal Bayhan, Petr Jabandziev, Saliha Kanik Yuksek, Adem Karbuz, Şadiye Kübra Tüter Öz, Gian Luigi Marseglia, Ozge Metin Akcan, Ahmet Osman Kılıç, Aslinur Ozkaya Parlakay, Maria Papadaki, Katerina Slaba, Esra Sevketoglu, Juan Valencia-Ramos, Aysun Yahşi, , Antonio Aguilera Guirao, Julián Álvarez Escudero, Antonio Antela López, Gema Barbeito Castiñeiras, Xabier Bello Paderne, Miriam Ben García, María Victoria Carral García, Miriam Cebey López, Amparo Coira Nieto, Mónica Conde Pájaro, José Javier Costa Alcalde, María José Currás Tuala, Ana Isabel Dacosta Urbieta, Blanca Díaz Esteban, María Jesús Domínguez Santalla, Cristina Fernández Pérez, Juan Fernández Villaverde, Cristóbal Galbán Rodríguez, José Luis García Allut, Luisa García Vicente, Elena Giráldez Vázquez, Alberto Gómez Carballa, José Gómez Rial, Francisco Javier González Barcala, Beatriz Guerra Liñares, Pilar Leboráns Iglesias, Beatriz Lence Massa, Marta Lendoiro Fuentes, Montserrat López Franco, Ana López Lago, Federico Martinón-Torres, Antonio Salas, Daniel Navarro De la Cruz, Eloína Núñez Masid, Juan Bautista Ortolá Devesa, Jacobo Pardo Seco, María Pazo Núñez, Marisa Pérez del Molino Bernal, Hugo Pérez Freixo, Lidia Piñeiro Rodríguez, Sara Pischedda, Manuel Portela Romero, Antonio Pose Reino, Gloria María Prada Hervella, Teresa Queiro Verdes, Lorenzo Redondo Collazo, Patricia Regueiro Casuso, Susana Rey García, Sara Rey Vázquez, Vanessa Riveiro Blanco, Irene Rivero Calle, Carmen Rivero Velasco, Nuria Rodríguez Núñez, Carmen Rodríguez-Tenreiro Sánchez, Eva Saborido Paz, José Miguel Sadiki Orayyou, Carla Saito Villanueva, Sonia Serén Fernández, Pablo Souto Sanmartín, Manuel Taboada Muñiz, Rocío Trastoy Pena, Mercedes Treviño Castellano, Luis Valdés Cuadrado, Pablo Varela García, María Soledad Vilas Iglesias, Sandra Viz Lasheras, Rocio Ferreiro-Iglesias, Iria Bastón-Rey, Cristina Calviño-Suárez, , Laurent Abel, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Jean-Laurent Casanova, Giorgio Casari, John Christodoulou, Aurélie Cobat, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Jacques Fellay, Carlos Flores, José Luis Franco, Antoine Froidure, Guy Gorochov, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Davood Mansouri, László Maródi, France Mentré, 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, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Anna Sediva, Mikko R.J. Seppänen, Mohammed Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, András N. Spaan, Helen C. Su, Ivan Tancevski, Stuart G. Tangye, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K.M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Qian Zhang, Shen-Ying Zhang, Pärt Peterson, Aurora Pujol, Romain Lévy, Pierre Quartier, Donald C. Vinh, Bertrand Boisson, Vivien Béziat, Shen-Ying Zhang, Alessandro Borghesi, Andrea Pession, Evangelos Andreakos, Nico Marr, Alexios-Fotios A. Mentis, Trine H. Mogensen, Carlos Rodríguez-Gallego, Pere Soler-Palacín, Roger Colobran, Vallo Tillmann, Bénédicte Neven, Sophie Trouillet-Assant, Petter Brodin, Laurent Abel, Emmanuelle Jouanguy, Qian Zhang, Federico Martinón-Torres, Antonio Salas, Alberto Gómez-Carballa, Luis I. Gonzalez-Granado, Kai Kisand, Satoshi Okada, Anne Puel, Aurélie Cobat, Jean-Laurent Casanova
Keywords:
Publication Date:
04 January 2024
Citation:
Bastard, P., Gervais, A., Taniguchi, M., Saare, L., Särekannu, K., Le Voyer, T., Philippot, Q., Rosain, J., Bizien, L., Asano, T., Garcia-Prat, M., Parra-Martínez, A., Migaud, M., Tsumura, M., Conti, F., Belot, A., Rivière, J. G., Morio, T., Tanaka, J., … Casanova, J.-L. (2024). Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children. Journal of Experimental Medicine, 221(2). https://doi.org/10.1084/jem.20231353
Abstract:
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω 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-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω 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-ω and/or IFN-α2.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
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, 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 solidarité 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 Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, the University of Paris Cité 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 Voyer were 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 Québec - Santé, Senior Clinician-Scientist scholar award. Q. Pan-Hammarström 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. Martinón-Torres]; Enterogen: PI19/01090 [F. Martinón-Torres]); OMI-COVI-VAC (PI22/00406 [F. Martinón-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 Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F. Martinón-Torres); GEN-COVID (IN845D 2020/23, F. Martinón-Torres) and Grupos de Referencia Competitiva (IIN607A2021/05, F. Martinón-Torres). The study was funded by ISCIII (COV20_01333, COV20_01334, PI16/00759, PI18/00223, PI19/00208, PI20/00876, and PI21/00211), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, EU), the Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC19/43, PIFIISC22/27), Grupo DISA (OA18/017), Fundación MAPFRE Guanarteme (OA21/131), Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). A. Pujol is supported by ACCI20-759 CIBERER, H2020 Marató 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.
Description:
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
ISSN:
0022-1007
1540-9538