Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths.

Bastard, Paul and Gervais, Adrian and Le Voyer, Tom and Rosain, Jérémie and Philippot, Quentin and Manry, Jérémy and Michailidis, Eleftherios and Hoffmann, Hans-Heinrich and Eto, Shohei and Garcia-Prat, Marina and Bizien, Lucy and Parra-Martínez, Alba and Yang, Rui and Haljasmägi, Liis and Migaud, Mélanie and Särekannu, Karita and Maslovskaja, Julia and de Prost, Nicolas and Tandjaoui-Lambiotte, Yacine and Luyt, Charles-Edouard and Amador-Borrero, Blanca and Gaudet, Alexandre and Poissy, Julien and Morel, Pascal and Richard, Pascale and Cognasse, Fabrice and Troya, Jesus and Trouillet-Assant, Sophie and Belot, Alexandre and Saker, Kahina and Garçon, Pierre and Rivière, Jacques G and Lagier, Jean-Christophe and Gentile, Stéphanie and Rosen, Lindsey B and Shaw, Elana and Morio, Tomohiro and Tanaka, Junko and Dalmau, David and Tharaux, Pierre-Louis and Sene, Damien and Stepanian, Alain and Megarbane, Bruno and Triantafyllia, Vasiliki and Fekkar, Arnaud and Heath, James R and Franco, José Luis and Anaya, Juan-Manuel and Solé-Violán, Jordi and Imberti, Luisa and Biondi, Andrea and Bonfanti, Paolo and Castagnoli, Riccardo and Delmonte, Ottavia M and Zhang, Yu and Snow, Andrew L and Holland, Steven M and Biggs, Catherine and Moncada-Vélez, Marcela and Arias, Andrés Augusto and Lorenzo, Lazaro and Boucherit, Soraya and Coulibaly, Boubacar and Anglicheau, Dany and Planas, Anna M and Haerynck, Filomeen and Duvlis, Sotirija and Nussbaum, Robert L and Ozcelik, Tayfun and Keles, Sevgi and Bousfiha, Ahmed A and El Bakkouri, Jalila and Ramirez-Santana, Carolina and Paul, Stéphane and Pan-Hammarström, Qiang and Hammarström, Lennart and Dupont, Annabelle and Kurolap, Alina and Metz, Christine N and Aiuti, Alessandro and Casari, Giorgio and Lampasona, Vito and Ciceri, Fabio and Barreiros, Lucila A and Dominguez-Garrido, Elena and Vidigal, Mateus and Zatz, Mayana and van de Beek, Diederik and Sahanic, Sabina and Tancevski, Ivan and Stepanovskyy, Yurii and Boyarchuk, Oksana and Nukui, Yoko and Tsumura, Miyuki and Vidaur, Loreto and Tangye, Stuart G and Burrel, Sonia and Duffy, Darragh and Quintana-Murci, Lluis and Klocperk, Adam and Kann, Nelli Y and Shcherbina, Anna and Lau, Yu-Lung and Leung, Daniel and Coulongeat, Matthieu and Marlet, Julien and Koning, Rutger and Reyes, Luis Felipe and Chauvineau-Grenier, Angélique and Venet, Fabienne and Monneret, Guillaume and Nussenzweig, Michel C and Arrestier, Romain and Boudhabhay, Idris and Baris-Feldman, Hagit and Hagin, David and Wauters, Joost and Meyts, Isabelle and Dyer, Adam H and Kennelly, Sean P and Bourke, Nollaig M and Halwani, Rabih and Sharif-Askari, Narjes Saheb and Dorgham, Karim and Sallette, Jérome and Sedkaoui, Souad Mehlal and AlKhater, Suzan and Rigo-Bonnin, Raúl and Morandeira, Francisco and Roussel, Lucie and Vinh, Donald C and Ostrowski, Sisse Rye and Condino-Neto, Antonio and Prando, Carolina and Bonradenko, Anastasiia and Spaan, András N and Gilardin, Laurent and Fellay, Jacques and Lyonnet, Stanislas and Bilguvar, Kaya and Lifton, Richard P and Mane, Shrikant and Anderson, Mark S and Boisson, Bertrand and Béziat, Vivien and Zhang, Shen-Ying and Vandreakos, Evangelos and Hermine, Olivier and Pujol, Aurora and Peterson, Pärt and Mogensen, Trine H and Rowen, Lee and Mond, James and Debette, Stéphanie and de Lamballerie, Xavier and Duval, Xavier and Mentré, France and Zins, Marie and Soler-Palacin, Pere and Colobran, Roger and Gorochov, Guy and Solanich, Xavier and Susen, Sophie and Martinez-Picado, Javier and Raoult, Didier and Vasse, Marc and Gregersen, Peter K and Piemonti, Lorenzo and Rodríguez-Gallego, Carlos and Notarangelo, Luigi D and Su, Helen C and Kisand, Kai and Okada, Satoshi and Puel, Anne and Jouanguy, Emmanuelle and Rice, Charles M and Tiberghien, Pierre and Zhang, Qian and Cobat, Aurélie and Abel, Laurent and Casanova, Jean-Laurent (2021) Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths. Science immunology, 6 (62). ISSN 2470-9468

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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.

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Sotirija Duvlis
Date Deposited: 20 Jun 2023 12:32
Last Modified: 20 Jun 2023 12:32

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