TY - JOUR
T1 - Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
AU - NIAID Immune Response to COVID Group
AU - Danish CHGE
AU - COVID Human Genetic Effort
AU - HGID Lab
AU - COVID-STORM Clinicians
AU - NH-COVAIR Study Group
AU - The Danish Blood Donor Study (DBDS)
AU - Imagine COVID-Group
AU - The Milieu Intérieur Consortium
AU - Amsterdam UMC Covid-19 Biobank
AU - CONSTANCES cohort
AU - 3C-Dijon Study
AU - Cerba HealthCare
AU - Etablissement du Sang study group
AU - CoV-Contact Cohort
AU - St James's Hospital, SARS CoV2 Interest group
AU - COVID Clinicians
AU - French COVID Cohort Study Group
AU - Bastard, Paul
AU - Gervais, Adrian
AU - Voyer, Tom Le
AU - Rosain, Jérémie
AU - Philippot, Quentin
AU - Manry, Jérémy
AU - Michailidis, Eleftherios
AU - Hoffmann, Hans Heinrich
AU - Eto, Shohei
AU - Garcia-Prat, Marina
AU - Bizien, Lucy
AU - Parra-Martínez, Alba
AU - Yang, Rui
AU - Haljasmägi, Liis
AU - Migaud, Mélanie
AU - Särekannu, Karita
AU - Maslovskaja, Julia
AU - De Prost, Nicolas
AU - Tandjaoui-Lambiotte, Yacine
AU - Luyt, Charles Edouard
AU - Amador-Borrero, Blanca
AU - Gaudet, Alexandre
AU - Poissy, Julien
AU - Morel, Pascal
AU - Richard, Pascale
AU - Cognasse, Fabrice
AU - Troya, Jesus
AU - Trouillet-Assant, Sophie
AU - Belot, Alexandre
AU - Saker, Kahina
AU - Garçon, Pierre
AU - Rivière, Jacques G.
AU - Lagier, Jean Christophe
AU - Gentile, Stéphanie
AU - Rosen, Lindsey B.
AU - Shaw, Elana
AU - Morio, Tomohiro
AU - Tanaka, Junko
AU - Dalmau, David
AU - Tharaux, Pierre Louis
AU - Sene, Damien
AU - Stepanian, Alain
AU - Megarbane, Bruno
AU - Triantafyllia, Vasiliki
AU - Fekkar, Arnaud
AU - Heath, James R.
AU - Franco, José Luis
AU - Anaya, Juan Manuel
AU - Solé-Violán, Jordi
AU - Dalgard, Clifton L.
N1 - Publisher Copyright:
© 2021 The Authors, some rights reserved.
PY - 2021/8/19
Y1 - 2021/8/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113517428&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.abl4340
DO - 10.1126/sciimmunol.abl4340
M3 - Article
C2 - 34413139
AN - SCOPUS:85113517428
SN - 2470-9468
VL - 6
JO - Science Immunology
JF - Science Immunology
IS - 62
M1 - eabl4340
ER -