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 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-Palacin, 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
Journal: The Journal of Experimental Medicine (2024)

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.