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

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 <70 years, 2.3\% between 70 and 80 years, and 6.3\% >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.