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

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.

DOI: 10.1084/jem.20231353, PMID: 38175961
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, 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