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

P Bastard, A Gervais, T Le Voyer, J Rosain… - Science …, 2021 - science.org
P Bastard, A Gervais, T Le Voyer, J Rosain, Q Philippot, J Manry, E Michailidis
Science immunology, 2021science.org
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 …
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.
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