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

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.

• Autores: Franco Restrepo, José Luis; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Rosain, Jérémie; Philippot, Quentin; Manry, Jérémy; Michailidis, Eleftherios; Hoffmann, Hans Heinrich; Eto, Shohei; Garcia Prat, Marina; Bizien, Lucy; Parra Martínez, Alba; Yang, Rui; Haljasmägi, Liis; Migaud, Mélanie; Särekannu, Karita; Maslovskaja, Julia; de Prost, Nicolas; Tandjaoui Lambiotte, Yacine; Luyt, Charles Edouard; Amador Borrero, Blanca; Gaudet, Alexandre; Poissy, Julien; Morel, Pascal; Richard, Pascale; Cognasse, Fabrice; Troya, Jesus; Trouillet Assant, Sophie; Belot, Alexandre; Saker, Kahina; Garçon, Pierre; Rivière, Jacques; Lagier, Jean Christophe; Gentile, Stéphanie; Rosen, Lindsey B.; Shaw, Elana; Morio, Tomohiro; Tanaka, Junko; Dalmau, David; Tharaux, Pierre Louis; Sene, Damien; Stepanian, Alain; Megarbane, Bruno; Triantafyllia, Vasiliki; Fekkar, Arnaud; Heath, James R.; Anaya, Juan Manuel; Solé Violán, Jordi; Imberti, Luisa; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Delmonte, Ottavia M.; Zhang, Yu; Snow, Andrew L.; Holland, Steven M.; Biggs, Catherine; Moncada Vélez, Marcela; Arias Sierra, Andrés Augusto; Lorenzo, Lazaro; Boucherit, Soraya; Coulibaly, Boubacar; Anglicheau, Dany; Planas, Anna M; Haerynck, Filomeen; Duvlis, Sotirija; Nussbaum, Robert L.; Ozcelik, Tayfun; Keles, Sevgi; Bousfiha, Ahmed A.; El Bakkouri, Jalila; Ramírez Santana, Carolina; Paul, Stéphane; Pan Hammarström, Qiang; Hammarström, Lennart; Dupont, Annabelle; Kurolap, Alina; Metz, Christine N.; Aiuti, Alessandro; AlKhater, Suzan; Arrestier, Romain; Baris Feldman, Hagit; Barreiros, Lucila A.; Bilguvar, Kaya; Boyarchuk, Oksana; Bourke, Nollaig M.; Burrel, Sonia; Casari, Giorgio; Chauvineau Grenier, Angélique; Ciceri, Fabio; Condino Neto, Antonio; Coulongeat, Matthieu; Czerkowicz, Jakub; Darragh, Duffy; Domínguez Garrido, Elena; Dorgham, Karim; Dyer, Adam H.; Fellay, Jacques; Gilardin, Laurent; Hagin, David; Halwani, Rabih; Isabelle, Meyts; Joost, Wauters; Kann, Nelli Y; Karakaya, Mahmut; Klocperk, Adam; Lampasona, Vito; Lau, Yu Lung; Leung, Daniel; Lifton, Richard P.; Loreto, Vidaur; Lucie, Roussel; Marlet, Julien; Mehlal, Sedkaoui Souad; Nussenzweig, Michel C; Miyuki, Tsumura; Monneret, Guillaume; Morandeira, Francisco; Narjes Saheb, Sharif-Askari; Prando, Carolina; Quintana Murci, Lluis; Rigo Bonnin, Raúl; Reyes, Luis Felipe; Rye Ostrowski, Sisse; Saheb, Sharif-Askari Narjes; Sahanic, Sabina; Sallette, Jérome; Kennelly, Sean P.; Shcherbina, Anna; Shrikant, Mane; Spaan, András N.; Stepanovskyy, Yurii; Tangye, Stuart G; Tancevski, Ivan; Venet, Fabienne; Vidigal, Mateus; Vinh, Donald C.; Wauters, Joost; Nukui, Yoko
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2021
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40974
• Acceso en línea: https://hdl.handle.net/10495/40974
• Palabra clave: Antibodies, Neutralizing; Anticuerpos Neutralizantes; Autoantibodies; Autoanticuerpos; COVID-19; Case-Control Studies; Estudios de Casos y Controles; Critical Illness; Enfermedad Crítica; Immunoglobulin G; Immunoglobulina G; Interferon Type I; Interferón Tipo I; Interferon-alpha; Interferón-alfa; Aged, 80 and over; Anciano de 80 o más Años; Middle Aged; Persona de Mediana Edad; https://id.nlm.nih.gov/mesh/D057134; https://id.nlm.nih.gov/mesh/D001323; https://id.nlm.nih.gov/mesh/D000086382; https://id.nlm.nih.gov/mesh/D016022; https://id.nlm.nih.gov/mesh/D016638; https://id.nlm.nih.gov/mesh/D007074; https://id.nlm.nih.gov/mesh/D007370; https://id.nlm.nih.gov/mesh/D007370; https://id.nlm.nih.gov/mesh/D016898; https://id.nlm.nih.gov/mesh/D000369; https://id.nlm.nih.gov/mesh/D008875
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/