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The Risk of COVID-19 Death is Much Greater and Age-Dependent with Type I IFN Autoantibodies

Jérémy Manry,Paul Bastard,Adrian Gervais,Tom Le Voyer,Jérémie Rosain,Quentin Philippot,Eleftherios Michailidis,Hans-Heinrich Hoffmann,Shohei Eto,Marina García-Prat,Lucy Bizien,Alba Parra-Martínez,Rui Yang,Liis Haljasmägi,Mélanie Migaud,Karita Särekannu,Julia Maslovskaja,Nicolas de Prost,Yacine Tandjaoui-Lambiotte,Charles‐Édouard Luyt,Blanca Amador-Borrero,Alexandre Gaudet,Julien Poissy,Pascal Morel,Pascale Richard,Fabrice Cognasse, Jesús Troya,Sophie Trouillet‐Assant,Alexandre Bélot,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 Sène,Alain Stépanian,Bruno Mégarbane,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,Zhang Yu,Andrew L. Snow,Steve Holland,Catherine M. Biggs,Marcela Moncada-Vélez,Andrés A. Arias,Lazaro Lorenzo,Soraya Boucherit,Dany Anglicheau,Anna M. Planas,Filomeen Haerynck,Sotirija Duvlis,Robert L. Nussbaum,Tayfun Ozcelik,Sevgi Keleş,Aziz Bousfiha,Jalila El Bakkouri,Carolina Ramírez-Santana,Stéphane Paul, Qiang Pan‐Hammarström,Lennart Hammarström,Annabelle Dupont,Alina Kurolap,Christine N. Metz,Alessandro Aiuti,Giorgio Casari,Vito Lampasona,Fabio Ciceri,Lucila Akune Barreiros,Elena Domínguez‐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,Lluís 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,Seán Kennelly,Nollaig M. Bourke,Rabih Halwani,Fatemeh Saheb Sharif‐Askari,Karim Dorgham,Jérôme Sallette,Souad Mehlal-Sedkaoui,Suzan A. AlKhater,Raül Rigo-Bonnin,Francisco Morandeira,Lucie Roussel,Donald C. Vinh,Christian Erikstrup, Antônio Condino‐Neto,Carolina Prando,Анастасія Бондаренко,András N. Spaan,Laurent Gilardin,Jacques Fellay,Stanislas Lyonnet,Kaya Bilgüvar,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 J. Mond,Stéphanie Debette,Xavier de-Lamballerie,Charles Burdet,Lila Bouadma,Marie Zins,Pere Soler‐Palacín,Roger Colobran,Guy Gorochov,Xavier Solanich,Sophie Susen,Javier Martínez-Picado,Didier Raoult,Marc Vasse,Peter K. Gregersen,Carlos Rodríguez-Gallego,Lorenzo Piemonti,Luigi D. Notarangelo,Helen C. Su, Kai Kisand,Satoshi Okada,Anne Puel,Emmanuelle Jouanguy,Charles M. Rice,Pierre Tiberghien,Qian Zhang,Jean‐Laurent Casanova,Laurent Abel,Aurélie Cobat

Research Square (Research Square)(2022)

Cited 80|Views7
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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.
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Immunity
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