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

Identifier:  imarina:9243261

Handle: https://hdl.handle.net/20.500.11797/imarina9243261

Authors:  Bastard P; Gervais A; Voyer TL; Rosain J; Philippot Q; Manry J; Michailidis E; Hoffmann HH; Eto S; Garcia-Prat M; Bizien L; Parra-Martínez A; Yang R; Haljasmägi L; Migaud M; Särekannu K; Maslovskaja J; De Prost N; Tandjaoui-Lambiotte Y; Luyt CE; Amador-Borrero B; Gaudet A; Poissy J; Morel P; Richard P; Cognasse F; Troya J; Trouillet-Assant S; Belot A; Saker K; Garçon P; Rivière JG; Lagier JC; Gentile S; Rosen LB; Shaw E; Morio T; Tanaka J; Dalmau D; Tharaux PL; Sene D; Stepanian A; Megarbane B; Triantafyllia V; Fekkar A; Heath JR; Franco JL; Anaya JM; Solé-Violán J; Imberti L; Biondi A; Bonfanti P; Castagnoli R; Delmonte OM; Zhang Y; Snow AL; Holland SM; Biggs CM; Moncada-Vélez M; Arias AA; Lorenzo L; Boucherit S; Coulibaly B; Anglicheau D; Planas AM; Haerynck F; Duvlis S; Nussbaum RL; Ozcelik T; Keles S; Bousfiha AA; El Bakkouri J; Ramirez-Santana C; Paul S; Pan-Hammarström Q; Hammarström L; Dupont A; Kurolap A; Metz CN; Aiuti A; Casari G; Lampasona V; Ciceri F; Barreiros LA; Dominguez-Garrido E; Vidigal M; Zatz M; Van De Beek D; Sahanic S; Tancevski I; Stepanovskyy Y; Boyarchuk O; Nukui Y; Tsumura M; Vidaur L; Tangye SG; Burrel S; Duffy D; Quintana-Murci L; Klocperk A

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.