The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

ABSTRACT: SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

• Autores: Franco Restrepo, José Luis; Manry, Jeremy; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Rosain, Jérémie; Philippot, Quentin; Michailidis, Eleftherios; Morio, Tomohiro; Haljasmägi, Liis; Särekannu, Karita; Amador-Borrero, Blanca; Puel, Anne; Tiberghien, Pierre; Zhang, Qian; Casanova, Jean Laurent; Abel, Laurent; Cobat, Aurélie; Gaudet, Alexandre; Morel, Pascal; Cognasse, Fabrice; Ramírez Santana, Carolina; Troya, Jesus; Trouillet-Assant, Sophie; Garçon, Pierre; Rivière, Jacques G; Lagier, Jean Christophe; Gentile, Stéphanie; Rosen, Lindsey; Shaw, Elana; Morio, Tomohiro; Tanaka, Junko; Paul, Stéphane; Dalmau, David; Tharaux, Pierre Louis; Sene, Damien; Stepanian, Alain; Triantafyllia, Vasiliki; Heath, James; Anaya Cabrera, Juan Manuel; Solé Violán, Jordi; Imberti, Luisa; Biondi, Andrea; Pan Hammarstrom, Qiang; Bonfanti, Paolo; Delmonte, Ottavia; Zhang, Yu; Snow, Andrew; Holland, Steve; Biggs, Catherine; Moncada Vélez, Marcela; Arias Sierra, Andrés Augusto; Lorenzo, Lázaro; Haerynck, Filomeen; Dupont, Annabelle; Duvlis, Sotirija; Nussbaum, Robert; Ozcelik, Tayfun; Keles, Sevgi; Bousfiha, Aziz; El Bakkouri, Jalila; Kurolap, Alina; Metz, Christine; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Ciceri, Fabio; Mehlal Sedkaoui, Souad; Barreiros, Lucila; Domínguez Garrido, Elena; Vidigal, Mateus; Koning, Rutger; Sahanic, Sabina; Tancevski, Ivan; Stepanovskyy, Yurii; Boyarchuk, Oksana; Nukui, Yoko; Tsumura, Miyuki; AlKhater, Suzan; Vidaur, Loreto; Tangye, Stuart; Burrel, Sonia; Duffy, Darragh; Quintana-Murci, Lluis; Klocperk, Adam; Kann, Nelli; Lau, Yu Lung; Leung, Daniel; Coulongeat, Matthieu; Morandeira, Francisco; Marlet, Julien; Reyes, Luis; Chauvineau Grenier, Angélique; Monneret, Guillaume; Nussenzweig, Michel; Arrestier, Romain; Boudhabhay, Idris; Hagin, David; Wauters, Joost; Meyts, Isabelle; Roussel, Lucie; Dyer, Adam; Kennelly, Sean; Bourke, Nollaig; Halwani, Rabih; Dorgham, Karim; Sallette, Jérôme; Vinh, Donald; Erikstrup, Christian; Condino Neto, Antonio; Prando, Carolina; Spaan, András; Gilardin, Laurent; de Prost, Nicolas; Fellay, Jacques; Lyonnet, Stanislas; Bilguvar, Kaya; Lifton, Richard; Anderson, Mark; Andreakos, Evangelos; Hermine, Olivier; Pujol, Aurora; Peterson, Pärt; Mogensen, Trine Hyrup; Tandjaoui-Lambiotte, Yacine; Rowen, Lee; Mond, James; Debette, Stéphanie; deLamballerie, Xavier; Burdet, Charles; Bouadma, Lila; Zins, Marie; Soler Palacin, Pere; Colobran, Roger; Gorochov, Guy; Luyt, Charles Edouard; Solanich, Xavier; Martínez Picado, Javier; Raoult, Didier; Vasse, Marc; Gregersen, Peter; Rodríguez Gallego, Carlos; Piemonti, Lorenzo; Notarangelo, Luigi; Su, Helen; Kisand, Kai
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40507
• Acceso en línea: https://hdl.handle.net/10495/40507
• Palabra clave: Factores de Edad; Age Factors; Anciano de 80 o más Años; Aged, 80 and over; Anticuerpos Neutralizantes; Antibodies, Neutralizing; Autoanticuerpos; Autoantibodies; Autoinmunidad; Autoimmunity; COVID-19; Interferón Tipo I; Interferon Type I; SARS-CoV-2; https://id.nlm.nih.gov/mesh/D000367; https://id.nlm.nih.gov/mesh/D000369; https://id.nlm.nih.gov/mesh/D057134; https://id.nlm.nih.gov/mesh/D001323; https://id.nlm.nih.gov/mesh/D015551; https://id.nlm.nih.gov/mesh/D000086382; https://id.nlm.nih.gov/mesh/D007370; https://id.nlm.nih.gov/mesh/D000086402
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/