The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Manry, Jérémy and Bastard, Paul and Gervais, Adrian and Le Voyer, Tom and Rosain, Jérémie and Philippot, Quentin 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, Jesús 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 Mégarbane, 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 M and Moncada-Vélez, Marcela and Arias, Andrés Augusto and Lorenzo, Lazaro and Boucherit, Soraya and Anglicheau, Dany and Planas, Anna M and Haerynck, Filomeen and Duvlis, Sotirija 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, Fatemeh Saheb and Dorgham, Karim and Sallette, Jérôme and Sedkaoui, Souad Mehlal and AlKhater, Suzan and Rigo-Bonnin, Raúl and Morandeira, Francisco and Roussel, Lucie and Vinh, Donald C and Erikstrup, Christian and Condino-Neto, Antonio and Prando, Carolina and Bondarenko, 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 Andreakos, 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 Burdet, Charles and Bouadma, Lila 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 Casanova, Jean-Laurent and Abel, Laurent and Cobat, Aurélie (2022) The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proceedings of the National Academy of Sciences of the United States of America, 119 (21). e2200413119. ISSN 1091-6490

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

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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