| Contributors: |
Bastard, P; Gervais, A; Voyer, Tl; Rosain, J; Philippot, Q; Manry, J; Michailidis, E; Hoffmann, H-; Eto, S; Garcia-Prat, M; Bizien, L; Parra-Martinez, A; Yang, R; Haljasmagi, L; Migaud, M; Sarekannu, K; Maslovskaja, J; De Prost, N; Tandjaoui-Lambiotte, Y; Luyt, C-; Amador-Borrero, B; Gaudet, A; Poissy, J; Morel, P; Richard, P; Cognasse, F; Troya, J; Trouillet-Assant, S; Belot, A; Saker, K; Garcon, P; Riviere, Jg; Lagier, J-; Gentile, S; Rosen, Lb; Shaw, E; Morio, T; Tanaka, J; Dalmau, D; Tharaux, P-; Sene, D; Stepanian, A; Megarbane, B; Triantafyllia, V; Fekkar, A; Heath, Jr; Franco, Jl; Anaya, J-; Sole-Violan, J; Imberti, L; Biondi, A; Bonfanti, P; Castagnoli, R; Delmonte, Om; Zhang, Y; Snow, Al; Holland, Sm; Biggs, Cm; Moncada-Velez, 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-Hammarstrom, Q; Hammarstrom, 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 |
| Description: |
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 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 1,124 deceased patients (aged 20 days-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 subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -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 subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 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. |