: 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 <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.

Bastard, P., Gervais, A., Voyer, T.l., Rosain, J., Philippot, Q., Manry, J., et al. (2021). Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. SCIENCE IMMUNOLOGY, 6(62) [10.1126/sciimmunol.abl4340].

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

Novelli G.;
2021-08-01

Abstract

: 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 <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.
ago-2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - GENETICA MEDICA
English
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Neutralizing
Autoantibodies
COVID-19
Case-Control Studies
Child
Child, Preschool
Critical Illness
Humans
Immunoglobulin G
Infant
Infant, Newborn
Interferon Type I
Interferon-alpha
Middle Aged
Young Adult
Bastard, P., Gervais, A., Voyer, T.l., Rosain, J., Philippot, Q., Manry, J., et al. (2021). Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. SCIENCE IMMUNOLOGY, 6(62) [10.1126/sciimmunol.abl4340].
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; 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