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

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DOI

  • Jérémy Manry, Universite Paris 5, Université de Paris
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  • Paul Bastard, Universite Paris 5, Université de Paris, Rockefeller University
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  • Adrian Gervais, Universite Paris 5, Université de Paris
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  • Tom Le Voyer, Universite Paris 5, Université de Paris
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  • Jérémie Rosain, Universite Paris 5, Université de Paris
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  • Quentin Philippot, Universite Paris 5, Université de Paris
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  • Eleftherios Michailidis, Rockefeller University
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  • Hans Heinrich Hoffmann, Rockefeller University
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  • Shohei Eto, Hiroshima University
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  • Marina Garcia-Prat, Autonomous University of Barcelona
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  • Lucy Bizien, Universite Paris 5, Université de Paris
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  • Alba Parra-Martínez, Autonomous University of Barcelona
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  • Rui Yang, Rockefeller University
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  • Liis Haljasmägi, University of Tartu
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  • Mélanie Migaud, Universite Paris 5, Université de Paris
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  • Karita Särekannu, University of Tartu
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  • Julia Maslovskaja, University of Tartu
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  • Nicolas de Prost, Hopital Henri Mondor
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  • Yacine Tandjaoui-Lambiotte, Hopital Avicenne
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  • Charles Edouard Luyt, Sorbonne Université, Institute of Cardiometabolism and Nutrition
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  • Blanca Amador-Borrero, Université de Paris
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  • Alexandre Gaudet, Université de Lille
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  • Julien Poissy, Université de Lille
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  • Pascal Morel, Etablissement Francais du Sang, Universite de Franche-Comte
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  • Pascale Richard, Etablissement Francais du Sang
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  • Fabrice Cognasse, Universite Jean Monnet Saint-Etienne, Etablissement Francais du Sang
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  • Jesús Troya, Complutense University of Madrid
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  • Sophie Trouillet-Assant, Hospices Civils de Lyon, École Normale Supérieure de Lyon, Centre Hospitalier Lyon-Sud
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  • Alexandre Belot, Hospices Civils de Lyon, École Normale Supérieure de Lyon, National Referee Centre for Rheumatic
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  • Kahina Saker, Hospices Civils de Lyon, École Normale Supérieure de Lyon
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  • Pierre Garçpn, Grand Hôpital de l’Est Francilien Site de Marne-La-Vallée
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  • Jacques G. Rivière, Autonomous University of Barcelona
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  • Jean Christophe Lagier, Aix-Marseille Université
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  • Stéphanie Gentile, AP-HM Assistance Publique - Hopitaux de Marseille, Aix-Marseille Université
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  • Lindsey B. Rosen, National Institutes of Health
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  • Elana Shaw, National Institutes of Health
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  • Tomohiro Morio, Graduate School of Medical and Dental Sciences
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  • Junko Tanaka, Hiroshima University
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  • David Dalmau, University of Barcelona, Fundació Docència i Recerca Mutua Terrassa
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  • Pierre Louis Tharaux, Université de Paris
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  • Damien Sene, Université de Paris
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  • Alain Stepanian, Université de Paris
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  • Bruno Mégarbane, Université de Paris
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  • Vasiliki Triantafyllia, Academy of Athens
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  • Arnaud Fekkar, Universite Paris 5, AP-HP Assistance Publique - Hopitaux de Paris
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  • James R. Heath, Institute for Systems Biology
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  • José Luis Franco, Universidad de Antioquia
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  • Christian Erikstrup
  • Trine H. Mogensen
  • Jean Laurent Casanova
  • Amsterdam UMC Covid-19 Biobank Investigators
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  • COVID Human Genetic Effort
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  • CP-COVID-19 Group
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  • CONSTANCES cohort
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  • 3C-Dijon Study
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  • Cerba Health-Care
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  • Etablissement Français du Sang Study group
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  • HGID Lab
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  • COVID Clinicians
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  • COVID-STORM Clinicians
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  • NIAID Immune Response to COVID Group
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  • NH-COVAIR Study Group
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  • Danish CHGE
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  • Danish Blood Donor Study
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  • St. James's Hospital, SARS CoV2 Interest Group
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  • French COVID Cohort Study Group
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  • Imagine COVID Group
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  • The Milieu Intérieur Consortium
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  • CoV-Contact Cohort

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.

Original languageEnglish
Article numbere2200413119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue21
Number of pages10
ISSN0027-8424
DOIs
Publication statusPublished - May 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 the Author(s).

    Research areas

  • autoantibodies, COVID-19, infection fatality rate, relative risk, type I IFNs

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