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



Bastard, Paul, Gervais, Adrian ORCID: 0000-0002-1083-5787, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherios ORCID: 0000-0002-9907-4346, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina ORCID: 0000-0001-5387-1908
et al (show 191 more authors) (2021) Autoantibodies neutralizing type I IFNs are present in <b>~</b>4% of uninfected individuals over 70 years old and account for <b>~</b>20% of COVID-19 deaths. Science immunology, 6 (62). eabl4340 - ?.

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Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 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 1,124 deceased patients (aged 20 days-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-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω 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 subjects 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-β 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.

Item Type: Article
Uncontrolled Keywords: 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, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank Investigators, COVID Human Genetic Effort, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement du Sang study group, Humans, Critical Illness, Immunoglobulin G, Interferon Type I, Interferon-alpha, Autoantibodies, Case-Control Studies, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Infant, Infant, Newborn, Young Adult, Antibodies, Neutralizing, COVID-19
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 04 May 2022 09:50
Last Modified: 08 Sep 2022 11:54
DOI: 10.1126/sciimmunol.abl4340
Open Access URL: https://doi.org/10.1126/sciimmunol.abl4340
URI: https://livrepository.liverpool.ac.uk/id/eprint/3154270