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

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The Milieu Intérieur Consortium , CoV-Contact Cohort , Amsterdam UMC Covid-19 Biobank Investigators , COVID Human Genetic Effort , CONSTANCES cohort , 3C-Dijon Study , Cerba HealthCare , Etablissement du Sang study group , HGID Lab , COVID Clinicians , COVID-STORM Clinicians , NIAID Immune Response to COVID Group , NH-COVAIR Study Group , Danish CHGE , Danish Blood Donor Study , St. James’s Hospital SARS CoV2 Interest group , French COVID Cohort Study Group , Imagine COVID Group , Bastard , P , Gervais , A , Le Voyer , T & Seppänen , M R J 2021 , ' Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths ' , Science immunology , vol. 6 , no. 62 , 4340 . https://doi.org/10.1126/sciimmunol.abl4340

Title: Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Author: The Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank Investigators; COVID Human Genetic Effort; CONSTANCES cohort; 3C-Dijon Study; Cerba HealthCare; Etablissement du Sang study group; HGID Lab; COVID Clinicians; COVID-STORM Clinicians; NIAID Immune Response to COVID Group; NH-COVAIR Study Group; Danish CHGE; Danish Blood Donor Study; St. James’s Hospital SARS CoV2 Interest group; French COVID Cohort Study Group; Imagine COVID Group; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Seppänen, Mikko R. J.
Contributor organization: Children's Hospital
HUS Children and Adolescents
Clinicum
Department of Medicine
Infektiosairauksien yksikkö
HUS Inflammation Center
Date: 2021-08-19
Language: eng
Number of pages: 26
Belongs to series: Science immunology
ISSN: 2470-9468
DOI: https://doi.org/10.1126/sciimmunol.abl4340
URI: http://hdl.handle.net/10138/340517
Abstract: 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 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.
Description: Publisher Copyright: © 2021 The Authors, some rights reserved.
Subject: 3121 General medicine, internal medicine and other clinical medicine
MYASTHENIA-GRAVIS PATIENTS
DISTINCT FUNCTIONS
ANTIBODIES
INTERFERON
ALPHA
AUTOIMMUNITY
ANTINUCLEAR
IMMUNITY
PATIENT
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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