Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Authors: Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Jérémy Manry, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, Lucy Bizien, Alba Parra-Martínez, Rui Yang, Liis Haljasmägi, Mélanie Migaud, Karita Särekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles-Edouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesus Troya, Sophie Trouillet-Assant, Alexandre Belot, Kahina Saker, Pierre Garçon, Jacques G. Rivière, Jean-Christophe Lagier, Stéphanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre-Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Megarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, José Luis Franco, Juan-Manuel Anaya, Jordi Solé-Violán, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada-Vélez, Andrés Augusto Arias, Lazaro Lorenzo, Soraya Boucherit, Boubacar Coulibaly, Dany Anglicheau, Anna M. Planas, Filomeen Haerynck, Sotirija Duvlis, Robert L. Nussbaum, Tayfun Ozcelik, Sevgi Keles, Ahmed A. Bousfiha, Jalila El Bakkouri, Carolina Ramirez-Santana, Stéphane Paul, Qiang Pan-Hammarström, Lennart Hammarström, Annabelle Dupont, Alina Kurolap, Christine N. Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila A. Barreiros, Elena Dominguez-Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yurii Stepanovskyy, Oksana Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluis Quintana-Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, Yu-Lung Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angélique Chauvineau-Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris-Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Sean P. Kennelly, Nollaig M. Bourke, Rabih Halwani, Narjes Saheb Sharif-Askari, Karim Dorgham, Jérome Sallette, Souad Mehlal Sedkaoui, Suzan AlKhater, Raúl Rigo-Bonnin, Francisco Morandeira, Lucie Roussel, Donald C. Vinh, Sisse Rye Ostrowski, Antonio Condino-Neto, Carolina Prando, Anastasiia Bondarenko, András N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilguvar, Richard P. Lifton, Shrikant Mane, Mark S. Anderson, Bertrand Boisson, Vivien Béziat, Shen-Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Pärt Peterson, Trine H. Mogensen, Lee Rowen, James Mond, Stéphanie Debette, Xavier de Lamballerie, Xavier Duval, France Mentré, Marie Zins, Pere Soler-Palacin, Roger Colobran, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martinez-Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodríguez-Gallego, Luigi D. Notarangelo, Helen C. Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Aurélie Cobat, Laurent Abel, Jean-Laurent Casanova
Journal: Science Immunology (2021)

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.