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  4. Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected individuals over 70 years old and account for similar to 20% of COVID-19 deaths
 
research article

Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected individuals over 70 years old and account for similar to 20% of COVID-19 deaths

Bastard, Paul
•
Gervais, Adrian
•
Le Voyer, Tom
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August 1, 2021
Science Immunology

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.

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Type
research article
DOI
10.1126/sciimmunol.abl4340
Web of Science ID

WOS:000695969700002

Author(s)
Bastard, Paul
Gervais, Adrian
Le Voyer, Tom
Rosain, Jeremie
Philippot, Quentin
Manry, Jeremy
Michailidis, Eleftherios
Hoffmann, Hans-Heinrich
Eto, Shohei
Garcia-Prat, Marina
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Date Issued

2021-08-01

Publisher

AMER ASSOC ADVANCEMENT SCIENCE

Published in
Science Immunology
Volume

6

Issue

62

Article Number

eabl4340

Subjects

Immunology

•

Immunology

•

myasthenia-gravis patients

•

distinct functions

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antibodies

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interferon

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alpha

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autoimmunity

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antinuclear

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immunity

•

patient

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPFELLAY  
Available on Infoscience
October 9, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/182090
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