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

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Jeremy Manry
Adrian Gervais
Shohei Eto
Marina Garcia-Prat
Rui Yang
Liis Haljasmägi
Karita Särekannu
Julia Maslovskaja
Nicolas de Prost
Yacine Tandjaoui-Lambiotte
Sophie Trouillet-Assant
Alexandre Belot
Kahina Saker
Lindsey Rosen
Elana Shaw
David Dalmau
James Heath
Juan-Manuel Anaya
Andrea Biondi
  • Function : Author
Catherine Biggs
Lazaro Lorenzo
Soraya Boucherit
Dany Anglicheau
Anna Planas
Filomeen Haerynck
Sotirija Duvlis
Robert Nussbaum
Tayfun Ozcelik
Qiang Pan-Hammarstrom
Elena Dominguez-Garrido
Diederik van de Beek
Yoko Nukui
Loreto Vidaur
Stuart Tangye
Sonia Burrel
Lluis Quintana-Murci
Yu-Lung Lau
Daniel Leung
Rutger Koning
Fabienne Venet
Guillaume Monneret
Michel Nussenzweig
David Hagin
Isabelle Meyts
Adam Dyer
Sean Kennelly
  • Function : Author
Nollaig Bourke
Rabih Halwani
Suzan Alkhater
Christian Erikstrup
András Spaan
Laurent Gilardin
Jacques Fellay
Kaya Bilguvar
Shrikant Mane
Mark Anderson
Bertrand Boisson
Shen-Ying Zhang
Evangelos Andreakos
Pärt Peterson
Trine Hyrup Mogensen
James Mond
  • Function : Author
Stéphanie Debette
Lila Bouadma
  • Function : Author
Kai Kisand
Satoshi Okada
Emmanuelle Jouanguy
Charles Rice
Pierre Tiberghien
Qian Zhang
Jean-Laurent Casanova
Laurent Abel

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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Dates and versions

pasteur-03610523 , version 1 (16-03-2022)

Licence

Attribution - CC BY 4.0

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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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