Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
Authors: Bastard Paul , Gervais Adrian , Taniguchi Maki , Saare Liisa , Särekannu Karita , Le Voyer Tom , Philippot Quentin , Rosain Jérémie , Bizien Lucy , Asano Takaki , Garcia-Prat Marina , Parra-Martínez Alba , Migaud Mélanie , Tsumura Miyuki , Conti Francesca , Belot Alexandre , Rivière Jacques G. , Morio Tomohiro , Tanaka Junko , Javouhey Etienne , Haerynck Filomeen , Duvlis Sotirija , Ozcelik Tayfun , Keles Sevgi , Tandjaoui-Lambiotte Yacine , Escoda Simon , Husain Maya , Pan-Hammarström Qiang , Hammarström Lennart , Ahlijah Gloria , Abi Haidar Anthony , Soudee Camille , Arseguel Vincent , Abolhassani Hassan , Sahanic Sabina , Tancevski Ivan , Nukui Yoko , Hayakawa Seiichi , Chrousos George P. , Michos Athanasios , Tatsi Elizabeth-Barbara , Filippatos Filippos , Rodriguez-Palmero Agusti , Troya Jesus , Tipu Imran , Meyts Isabelle , Roussel Lucie , Ostrowski Sisse Rye , Schidlowski Laire , Prando Carolina , Condino-Neto Antonio , Cheikh Nathalie , Bousfiha Ahmed A. , El Bakkouri Jalila ,   COVID Clinicians, Aguilera-Albesa Sergio , AlKhater Suzan A. , Alkan Gulsum , Castagnoli Riccardo , Cyrus Cyril , Elmas Bozdemir Sefika , Emiroglu Melike , Gulhan Belgin , Erdeniz Emine Hafize , Hatipoglu Nevin , Bayhan Gülsün Iclal , Jabandziev Petr , Kanik Yuksek Saliha , Karbuz Adem , Tüter Öz Şadiye Kübra , Marseglia Gian Luigi , Metin Akcan Ozge , Kılıç Ahmet Osman , Ozkaya Parlakay Aslinur , Papadaki Maria , Slaba Katerina , Sevketoglu Esra , Valencia-Ramos Juan , Yahşi Aysun ,   GEN-COVID Study Group, Aguilera Guirao Antonio , Álvarez Escudero Julián , Antela López Antonio , Barbeito Castiñeiras Gema , Bello Paderne Xabier , Ben García Miriam , Carral García María Victoria , Cebey López Miriam , Coira Nieto Amparo , Conde Pájaro Mónica , Costa Alcalde José Javier , Currás Tuala María José , Dacosta Urbieta Ana Isabel , Díaz Esteban Blanca , Domínguez Santalla María Jesús , Fernández Pérez Cristina , Fernández Villaverde Juan , Galbán Rodríguez Cristóbal , García Allut José Luis , García Vicente Luisa , Giráldez Vázquez Elena , Gómez Carballa Alberto , Gómez Rial José , González Barcala Francisco Javier , Guerra Liñares Beatriz , Leboráns Iglesias Pilar , Lence Massa Beatriz , Lendoiro Fuentes Marta , López Franco Montserrat , López Lago Ana , Martinón-Torres Federico , Salas Antonio , Navarro De la Cruz Daniel , Núñez Masid Eloína , Ortolá Devesa Juan Bautista , Pardo Seco Jacobo , Pazo Núñez María , Pérez del Molino Bernal Marisa , Pérez Freixo Hugo , Piñeiro Rodríguez Lidia , Pischedda Sara , Portela Romero Manuel , Pose Reino Antonio , Prada Hervella Gloria María , Queiro Verdes Teresa , Redondo Collazo Lorenzo , Regueiro Casuso Patricia , Rey García Susana , Rey Vázquez Sara , Riveiro Blanco Vanessa , Rivero Calle Irene , Rivero Velasco Carmen , Rodríguez Núñez Nuria , Rodríguez-Tenreiro Sánchez Carmen , Saborido Paz Eva , Sadiki Orayyou José Miguel , Saito Villanueva Carla , Serén Fernández Sonia , Souto Sanmartín Pablo , Taboada Muñiz Manuel , Trastoy Pena Rocío , Treviño Castellano Mercedes , Valdés Cuadrado Luis , Varela García Pablo , Vilas Iglesias María Soledad , Viz Lasheras Sandra , Ferreiro-Iglesias Rocio , Bastón-Rey Iria , Calviño-Suárez Cristina ,   COVID Human Genetic Effort, Abel Laurent , Aiuti Alessandro , Al-Muhsen Saleh , Al-Mulla Fahd , Amara Ali , Anderson Mark S. , Andreakos Evangelos , Arias Andrés A. , Arkin Lisa M. , Baris Feldman Hagit , Bastard Paul , Belot Alexandre , Biggs Catherine M. , Bogunovic Dusan , Bolze Alexandre , Bondarenko Anastasiia , Bousfiha Ahmed A. , Brodin Petter , Bryceson Yenan , Butte Manish J. , Casanova Jean-Laurent , Casari Giorgio , Christodoulou John , Cobat Aurélie , Colobran Roger , Condino-Neto Antonio , Constantinescu Stefan N. , Cooper Megan A. , Dalgard Clifton L. , Desai Murkesh , Drolet Beth A. , Duval Xavier , El Baghdadi Jamila , Eloy Philippine , Espinosa-Padilla Sara , Fellay Jacques , Flores Carlos , Franco José Luis , Froidure Antoine , Gorochov Guy , Gregersen Peter K. , Grimbacher Bodo , Haerynck Filomeen , Hagin David , Halwani Rabih , Hammarström Lennart , Heath James R. , Hsieh Elena W.Y. , Husebye Eystein , Imai Kohsuke , Itan Yuval , Jarvis Erich D. , Jouanguy Emmanuelle , Kaja Elżbieta , Karamitros Timokratis , Kisand Kai , Ku Cheng-Lung , Lau Yu-Lung , Ling Yun , Lucas Carrie L. , Mansouri Davood , Maródi László , Mentré France , Meyts Isabelle , Milner Joshua D. , Mironska Kristina , Mogensen Trine H. , Morio Tomohiro , Ng Lisa F.P. , Notarangelo Luigi D. , Novelli Antonio , Novelli Giuseppe , O’Farrelly Cliona , Okada Satoshi , Okamoto Keisuke , Ozcelik Tayfun , Pan-Hammarström Qiang , Pape Jean W. , Perez de Diego Rebeca , Perez-Tur Jordi , Perlin David S. , Pesole Graziano , Planas Anna M. , Prando Carolina , Pujol Aurora , Puel Anne , Quintana-Murci Lluis , Ramaswamy Sathishkumar , Renia Laurent , Resnick Igor , Rodríguez-Gallego Carlos , Sancho-Shimizu Vanessa , Sediva Anna , Seppänen Mikko R.J. , Shahrooei Mohammed , Shcherbina Anna , Slaby Ondrej , Snow Andrew L. , Soler-Palacín Pere , Soumelis Vassili , Spaan András N. , Su Helen C. , Tancevski Ivan , Tangye Stuart G. , Abou Tayoun Ahmad , Temel Şehime Gülsün , Thorball Christian , Tiberghien Pierre , Trouillet-Assant Sophie , Turvey Stuart E. , Furkan Uddin K.M. , Uddin Mohammed J. , van de Beek Diederik , Vinh Donald C. , von Bernuth Horst , Wauters Joost , Zatz Mayana , Zawadzki Pawel , Zhang Qian , Zhang Shen-Ying , Peterson Pärt , Pujol Aurora , Lévy Romain , Quartier Pierre , Vinh Donald C. , Boisson Bertrand , Béziat Vivien , Zhang Shen-Ying , Borghesi Alessandro , Pession Andrea , Andreakos Evangelos , Marr Nico , Mentis Alexios-Fotios A. , Mogensen Trine H. , Rodríguez-Gallego Carlos , Soler-Palacin Pere , Colobran Roger , Tillmann Vallo , Neven Bénédicte , Trouillet-Assant Sophie , Brodin Petter , Abel Laurent , Jouanguy Emmanuelle , Zhang Qian , Martinón-Torres Federico , Salas Antonio , Gómez-Carballa Alberto , Gonzalez-Granado Luis I. , Kisand Kai , Okada Satoshi , Puel Anne , Cobat Aurélie , Casanova Jean-Laurent 
Published: January 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.