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

Authors: Paul Bastard, Adrian Gervais, Maki Taniguchi, Liisa Saare, Karita Särekannu, Tom Le Voyer, Quentin Philippot, Jérémie Rosain, Lucy Bizien, Takaki Asano, Marina García-Prat, Alba Parra-Martínez, Mélanie Migaud, Miyuki Tsumura, Francesca Conti, Alexandre Bélot, Jacques G. Rivière, Tomohiro Morio, Junko Tanaka, Étienne Javouhey, Filomeen Haerynck, Sotiriјa Duvlis, Tayfun Özçelık, Sevgi Keleş, Yacine Tandjaoui-Lambiotte, Simon Escoda, M. Husain, Qiang Pan‐Hammarström, Lennart Hammarström, Gloria Ahlijah, A Haidar, Camille Soudée, Vincent Arseguel, Hassan Abolhassani, Sabina Sahanic, Ivan Tancevski, Yoko Nukui, Seiichi Hayakawa, George P. Chrousos, Athanasios Michos, Elizabeth‐Barbara Tatsi, Filippos Filippatos, Agustí Rodríguez‐Palmero, Jesús Troya, Imran Tipu, Isabelle Meyts, Lucie Roussel, Sisse Rye Ostrowski, Laire Schidlowski, Carolina Prando, Antônio Condino‐Neto, Nathalie Cheikh, Ahmed Aziz Bousfiha, Jalila El Bakkouri, Sergio Aguilera, Suzan A. AlKhater, Gülsüm Alkan, Riccardo Castagnoli, Cyril Cyrus, Şefika Elmas Bozdemir, Melike Emiroğlu, Belgi̇n Gülhan, Emine Hafize Erdeniz, Nevin Hatipoğlu, Gülsün Iclal Bayhan, Petr Jabandžiev, Saliha Kanık Yüksek, Adem Karbuz, Şadiye Kübra Tüter Öz, Gian Luigi Marseglia, Özge Metin Akcan, Ahmet Osman Kılıç, Aslınur Özkaya Parlakay, Maria Papadaki, Kateřina Slabá, Esra Şevketoğlu, Juan Valencia-Ramos, Aysun Yahşi, GEN-COVID Study Group, Antonio Aguilera Guirao, Julián Álvarez Escudero, Antonio Antela López, Gema Barbeito Castiñeiras, Xabier Bello Paderne, Mirian Ben García, María Victoria Carral García, Miriam Cebey‐López, Amparo Coira, M. 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 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, M. Castellano, Luis Valdés Cuadrado, Pablo Varela García, María Soledad Vilas Iglesias, Sandra Viz-Lasheras, Rocío Ferreiro‐Iglesias, Iria Bastón‐Rey, Cristina Suárez, COVID Human Genetic Effort, 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 Bélot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Анастасія Бондаренко, Ahmed Aziz Bousfiha, Petter Brodin, Yenan T. Bryceson, Manish J. Butte, Jean-Laurent Casanova, Giorgio Casari, John Christodoulou, Aurélie Cobat, Roger Colobrán, Antônio Condino‐Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Elva 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 S. Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng‐Lung Ku, YL Lau, Yun Ling, C. 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 Özçelık, Qiang Pan‐Hammarström, Jean W. Pape, Rebeca Pérez de Diego, Jordi Pérez‐Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluís Quintana‐Murci, Sathishkumar Ramaswamy, Laurent Rénia, Igor Resnick, Carlos Rodríguez‐Gallego, Vanessa Sancho‐Shimizu, Anna Šedivá, Mikko Seppänen, Mohammed Shahrooei, Anna Shcherbina, Ondřej Slabý, 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 Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Paweł Zawadzki, Qian Zhang, Shen‐Ying Zhang, Pärt Peterson, Aurora Pujol, Romain Lévy, Pierre Quartier, Donald C. Vinh, Bertrand Boisson, Vivien Béziat, Shen‐Ying Zhang, A. Borghesi, Andrea Pession, Evangelos Andreakos, Nico Marr, Alexios‐Fotios A. Mentis, Trine H. Mogensen, Carlos Rodríguez‐Gallego, Pere Soler‐Palacín, Roger Colobrán, Vallo Tillmann, Bénédicte Neven, Sophie Trouillet‐Assant, Petter Brodin, Laurent Abel, Emmanuelle Jouanguy, Qian Zhang, Federico Martinón‐Torres, Antonio Salas, Alberto Gómez‐Carballa, Luis Ignacio González‐Granado, Kai Kisand, Satoshi Okada, Anne Puel, Aurélie Cobat, Jean-Laurent Casanova - The Journal of Experimental Medicine 2024 cited by 39

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.