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Preprints, Working Papers, ...

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

Jeremy Manry 1, * Paul Bastard 1 Adrian Gervais Tom Le Voyer 1 Jérémie Rosain 1 Quentin Philippot 1 Eleftherios Michailidis 2 Hans-Heinrich Hoffmann 2 Shohei Eto 3 Marina Garcia-Prat 4 Lucy Bizien 1 Alba Parra-Martínez 4 Rui Yang 2 Liis Haljasmägi 5 Mélanie Migaud 1 Karita Särekannu 5 Julia Maslovskaja 5 Nicolas de Prost 6 Yacine Tandjaoui-Lambiotte 7 Charles-Edouard Luyt 8 Blanca Amador-Borrero 9 Alexandre Gaudet 10 Julien Poissy 10 Pascal Morel 11 Pascale Richard 11 Fabrice Cognasse 12 Jesus Troya 13 Sophie Trouillet-Assant 14 Alexandre Belot 14 Kahina Saker 14 Pierre Garçon 15 Jacques Rivière 16 Jean-Christophe Lagier 17 Stéphanie Gentile 18 Lindsey Rosen 19 Elana Shaw 19 Tomohiro Morio 20 Junko Tanaka 3 David Dalmau 21 Pierre-Louis Tharaux 22 Damien Sene 9 Alain Stepanian 9 Bruno Mégarbane 9, 22 Vasiliki Triantafyllia 23 Arnaud Fekkar 22 James Heath 24 Jose Franco 25 Juan-Manuel Anaya 26 Jordi Solé-Violán 27 Luisa Imberti 28 Andrea Biondi Paolo Bonfanti 29 Riccardo Castagnoli 19 Ottavia Delmonte 19 Yu Zhang 30 Andrew Snow 31 Steve Holland 30 Catherine Biggs 32 Marcela Moncada-Vélez 2 Andrés Arias 2 Lazaro Lorenzo 33 Soraya Boucherit 33 Dany Anglicheau 33 Anna Planas 34 Filomeen Haerynck 35 Sotirija Duvlis 36 Robert Nussbaum 37 Tayfun Ozcelik 38 Sevgi Keles 39 Aziz Bousfiha 40 Jalila El Bakkouri 41 Carolina Ramirez-Santana 26 Stéphane Paul 42 Qiang Pan-Hammarstrom 43 Lennart Hammarstrom 43 Annabelle Dupont 44, 22 Alina Kurolap 45 Christine Metz 46 Alessandro Aiuti 47 Giorgio Casari 48 Vito Lampasona 48 Fabio Ciceri 47 Lucila Barreiros 49 Elena Dominguez-Garrido 50 Mateus Vidigal 49 Mayana Zatz 49 Diederik van de Beek 51 Sabina Sahanic 52 Ivan Tancevski 52 Yurii Stepanovskyy 53 Oksana Boyarchuk 54 Yoko Nukui 20 Miyuki Tsumura 3 Loreto Vidaur 55 Stuart Tangye 56 Sonia Burrel 57 Darragh Duffy 58 Lluis Quintana-Murci 59 Adam Klocperk 60, 61 Nelli Kann 62 Anna Shcherbina 62 Yu-Lung Lau 63 Daniel Leung 63 Matthieu Coulongeat 64 Julien Marlet 65 Rutger Koning 51 Luis Reyes 66 Angélique Chauvineau-Grenier 67 Fabienne Venet 14 Guillaume Monneret 14 Michel Nussenzweig 2 Romain Arrestier 6 Idris Boudhabhay 33, 22 Hagit Baris-Feldman 45 David Hagin 68 Joost Wauters 69 Isabelle Meyts 70 Adam Dyer 71 Sean Kennelly 71 Nollaig Bourke 72 Rabih Halwani Fatemeh Sharif-Askari 73 Karim Dorgham 74 Jérôme Sallette 75 Souad Mehlal-Sedkaoui 75 Suzan Alkhater 76 Raúl Rigo-Bonnin 77 Francisco Morandeira 77 Lucie Roussel 78 Donald Vinh 78 Christian Erikstrup 79 Antonio Condino-Neto 49 Carolina Prando 80 Anastasiia Bondarenko 53 András Spaan 2 Laurent Gilardin 81 Jacques Fellay 82 Stanislas Lyonnet 33 Kaya Bilguvar 83 Richard Lifton 2 Shrikant Mane 83 Mark Anderson 84 Bertrand Boisson 2 Vivien Béziat 22 Shen-Ying Zhang Evangelos Andreakos 85 Olivier Hermine 22 Aurora Pujol 86 Pärt Peterson 5 Trine Hyrup Mogensen 79 Lee Rowen 24 James Mond Stéphanie Debette 87 Xavier Delamballerie 88 Charles Burdet 89 Lila Bouadma 90 Marie Zins 91, 92, 22 Pere Soler-Palacin 16 Roger Colobran 16 Guy Gorochov 57, 93 Xavier Solanich 77 Sophie Susen 94 Javier Martinez-Picado 95 Didier Raoult 88, 17 Marc Vasse 96 Peter Gregersen 46 Carlos Rodríguez-Gallego 27 Lorenzo Piemonti 48 Luigi Notarangelo 30 Helen Su 30 Kai Kisand 5 Satoshi Okada 3 Anne Puel 22 Emmanuelle Jouanguy 2 Charles Rice 2 Pierre Tiberghien 97 Qian Zhang 2 Jean-Laurent Casanova Laurent Abel 98 Aurélie Cobat 22
* Corresponding author
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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https://hal-pasteur.archives-ouvertes.fr/pasteur-03610523
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Submitted on : Wednesday, March 16, 2022 - 2:23:26 PM
Last modification on : Friday, May 20, 2022 - 11:06:22 AM

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Jeremy Manry, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, et al.. The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies. 2022. ⟨pasteur-03610523⟩

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