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