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

Jeremy Manry, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, 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 LuytBlanca 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 Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre-Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Mégarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James Heath, Jose Franco, Juan-Manuel Anaya, Jordi Solé-Violán, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia Delmonte, Yu Zhang, Andrew Snow, Steve Holland, Catherine Biggs, Marcela Moncada-Vélez, Andrés Arias, Lazaro Lorenzo, Soraya Boucherit, Dany Anglicheau, Anna Planas, Filomeen Haerynck, Sotirija Duvlis, Robert Nussbaum, Tayfun Ozcelik, Sevgi Keles, Aziz Bousfiha, Jalila El Bakkouri, Carolina Ramirez-Santana, Stéphane Paul, Qiang Pan-Hammarstrom, Lennart Hammarstrom, Annabelle Dupont, Alina Kurolap, Christine Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila 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 Tangye, Sonia Burrel, Darragh Duffy, Lluis Quintana-Murci, Adam Klocperk, Nelli Kann, Anna Shcherbina, Yu-Lung Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Reyes, Angélique Chauvineau-Grenier, Fabienne Venet, Guillaume Monneret, Michel Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris-Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam Dyer, Sean Kennelly, Nollaig Bourke, Rabih Halwani, Fatemeh Sharif-Askari, Karim Dorgham, Jérôme Sallette, Souad Mehlal-Sedkaoui, Suzan AlKhater, Raúl Rigo-Bonnin, Francisco Morandeira, Lucie Roussel, Donald Vinh, Christian Erikstrup, Antonio Condino-Neto, Carolina Prando, Anastasiia Bondarenko, András Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilguvar, Richard Lifton, Shrikant Mane, Mark Anderson, Bertrand Boisson, Vivien Béziat, Shen-Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Pärt Peterson, Trine Hyrup Mogensen, Lee Rowen, James Mond, Stéphanie Debette, Xavier deLamballerie, Charles Burdet, Lila Bouadma, Marie Zins, Pere Soler-Palacin, Roger Colobran, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martinez-Picado, Didier Raoult, Marc Vasse, Peter Gregersen, Carlos Rodríguez-Gallego, Lorenzo Piemonti, Luigi Notarangelo, Helen Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles Rice, Pierre Tiberghien, Qian Zhang, Jean-Laurent Casanova, Laurent Abel, Aurélie Cobat

Research output: Contribution to journalArticle

Abstract

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years 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. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Original languageEnglish (US)
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StatePublished - Jan 14 2022

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