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

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 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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 14, 2022
Source ID
10.21203/rs.3.rs-1225906/v1

Entities

People

  • Adam Dyer
  • Adam Klocperk
  • Adrian Gervais
  • Alain Stepanian
  • Alba Parra-martínez
  • Alessandro Aiuti
  • Alexandre Belot
  • Alexandre Gaudet
  • Alina Kurolap
  • Anastasiia Bondarenko
  • Andrea Biondi
  • Andres A Arias
  • Andrew L. Snow
  • András Spaan
  • Angélique Chauvineau-grenier
  • Anna M Planas
  • Anna Shcherbina
  • Annabelle Dupont
  • Anne Puel
  • Antonio Condino-neto
  • Arnaud Fekkar
  • Aurora Pujol
  • Aurélie Cobat
  • Aziz Bousfiha
  • Bertrand Boisson
  • Blanca Amador-borrero
  • Bruno Mégarbane
  • Carlos Rodríguez-Gallego
  • Carolina Prando
  • Carolina Ramirez-santana
  • Catherine Biggs
  • Charles Burdet
  • Charles M. Rice
  • Charles-edouard Luyt
  • Christian Erikstrup
  • Christine Metz
  • Damien Sene
  • Daniel Leung
  • Dany Anglicheau
  • Darragh Duffy
  • David Dalmau
  • David Hagin
  • Didier Raoult
  • Diederik van de Beek
  • Donald C Vinh
  • Elana Shaw
  • Eleftherios Michailidis
  • Elena Dominguez-garrido
  • Emmanuelle Jouanguy
  • Evangelos Andreakos
  • Fabienne Venet
  • Fabio Ciceri
  • Fabrice Cognasse
  • Fatemeh Sharif-askari
  • Filomeen Haerynck
  • Francisco Morandeira
  • Giorgio Casari
  • Guillaume Monneret
  • Guy Gorochov
  • Hagit Baris-feldman
  • Hans-Heinrich Hoffmann
  • Helen Su
  • Idris Boudhabhay
  • Isabelle Meyts
  • Ivan Tancevski
  • Jacques Fellay
  • Jacques G Rivière
  • Jalila El Bakkouri
  • James Mond
  • James R. Heath
  • Javier Martinez-Picado
  • Jean-Laurent Casanova
  • Jean-christophe Lagier
  • Jesus Troya
  • Joost Wauters
  • Jordi Solé-violán
  • Jose Luis Franco
  • Juan-Manuel Anaya
  • Julia Maslovskaja
  • Julien Marlet
  • Julien Poissy
  • Junko Tanaka
  • Jérémie Rosain
  • Jérémy Manry
  • Jérôme Sallette
  • Kahina Saker
  • Kai Kisand
  • Karim Dorgham
  • Karita Särekannu
  • Kaya Bilguvar
  • Laurent Abel
  • Laurent Gilardin
  • Lazaro Lorenzo
  • Lee Rowen
  • Lennart Hammarström
  • Liis Haljasmägi
  • Lila Bouadma
  • Lindsey Rosen
  • Lluís Quintana-Murci
  • Lorenzo Piemonti
  • Loreto Vidaur
  • Lucie Roussel
  • Lucila Barreiros
  • Lucy Bizien
  • Luigi D Notarangelo
  • Luis F Reyes
  • Luisa Imberti
  • Marc Vasse
  • Marcela Moncada-vélez
  • Marie Zins
  • Marina Garcia-prat
  • Mark Anderson
  • Mateus Vidigal
  • Matthieu Coulongeat
  • Mayana Zatz
  • Michel C. Nussenzweig
  • Miyuki Tsumura
  • Mélanie Migaud
  • Nelli Kann
  • Nicolas de Prost
  • Nollaig Bourke
  • Oksana Boyarchuk
  • Olivier Hermine
  • Ottavia Delmonte
  • Paolo Bonfanti
  • Pascal Morel
  • Pascale Richard
  • Paul Bastard
  • Pere Soler-Palacín
  • Peter K Gregersen
  • Pierre Garçon
  • Pierre Tiberghien
  • Pierre-Louis Tharaux
  • Pärt Peterson
  • Qian Zhang
  • Qiang Pan Hammarström
  • Quentin Philippot
  • Rabih Halwani
  • Raúl Rigo-bonnin
  • Riccardo Castagnoli
  • Richard Lifton
  • Robert L. Nussbaum
  • Roger Colobran
  • Romain Arrestier
  • Rui Yang
  • Rutger Koning
  • Sabina Sahanic
  • Satoshi Okada
  • Sean Kennelly
  • Sevgi Keleş
  • Shen-Ying Zhang
  • Shohei Eto
  • Shrikant M Mane
  • Sonia Burrel
  • Sophie Susen
  • Sophie Trouillet-assant
  • Soraya Boucherit
  • Sotirija Duvlis
  • Souad Mehlal-sedkaoui
  • Stanislas Lyonnet
  • Stephanie Debette
  • Steven M. Holland
  • Stuart Tangye
  • Stéphane Paul
  • Stéphanie Gentile
  • Suzan Alkhater
  • Tayfun Özçelik
  • Tom Le Voyer
  • Tomohiro Morio
  • Trine H Mogensen
  • Vasiliki Triantafyllia
  • Vito Lampasona
  • Vivien Béziat
  • Xavier Delamballerie
  • Xavier Solanich
  • Yacine Tandjaoui-Lambiotte
  • Yoko Nukui
  • Yu Zhang
  • Yu-lung Lau
  • Yurii Stepanovskyy

Organizations

  • Aarhus University
  • Academy of Athens
  • Aix-Marseille University
  • Assistance Publique – Hôpitaux de Paris
  • Avicenne Hospital
  • Bilkent University
  • Catalan Institution for Research and Advanced Studies
  • Charles University
  • CombiMatrix
  • Donostia Hospital
  • French Blood Establishment
  • French National Institute of Health and Medical Research
  • Garvan Institute of Medical Research
  • Ghent University
  • Hiroshima University
  • Institute for Systems Biology
  • IrsiCaixa
  • Karolinska Institutet
  • McGill University
  • McGill University Health Centre
  • Medical University of Innsbruck
  • Méditerranée Infection Foundation
  • National Institute of Allergy and Infectious Diseases
  • National Institutes of Health
  • Necker–Enfants Malades Hospital
  • Necmettin Erbakan University
  • Northwell Health
  • Our Lady of the Rosary University
  • Paris 8 University
  • Paris Diderot University
  • Pasteur Institute
  • Pitié-Salpêtrière Hospital
  • Shupyk National Healthcare University of Ukraine
  • Sorbonne University
  • Sorbonne Universités
  • Spanish National Research Council
  • Swiss Federal Institute of Technology in Lausanne
  • Tallaght Hospital
  • Tel Aviv University
  • The Feinstein Institute for Medical Research
  • The Rockefeller University
  • Tokyo Medical and Dental University
  • Tours University
  • Trinity College Dublin
  • UZ Leuven
  • Uniformed Services University of the Health Sciences
  • University of Antioquia
  • University of Barcelona
  • University of Bordeaux
  • University of California, San Francisco
  • University of Hong Kong
  • University of La Sabana
  • University of Lille
  • University of Milan-Bicocca
  • University of Paris
  • University of Sharjah
  • University of São Paulo
  • University of Tartu
  • Vall d'Hebron Hospital Universitari
  • Vita-Salute San Raffaele University
  • Yale University
  • hospices civils de lyon

Tags

Fields of Study

  • Medicine

Readers

  • Immunology
  • Infectious Disease/Epidemiology