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

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