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

NIAID Immune Response to COVID Group, Danish CHGE, COVID Human Genetic Effort, HGID Lab, COVID-STORM Clinicians, NH-COVAIR Study Group, The Danish Blood Donor Study (DBDS), Imagine COVID-Group, The Milieu Intérieur Consortium, Amsterdam UMC Covid-19 Biobank, CONSTANCES cohort, 3C-Dijon Study, Cerba HealthCare, Etablissement du Sang study group, CoV-Contact Cohort, St James's Hospital, SARS CoV2 Interest group, COVID Clinicians, French COVID Cohort Study Group

Research output: Contribution to journalArticlepeer-review

395 Scopus citations

Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω 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-α and/or IFN-ω (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-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-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 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-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.

Original languageEnglish
Article numbereabl4340
JournalScience Immunology
Volume6
Issue number62
DOIs
StatePublished - 19 Aug 2021
Externally publishedYes

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