Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected
individuals over 70 years old and account for similar to 20% of COVID-19 deaths
Bastard, Paul ✉; Gervais, Adrian; Le, Voyer Tom; Rosain, Jeremie; Philippot, Quentin; Manry, Jeremy; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Eto, Shohei; Garcia-Prat, Marina; Bizien, Lucy; Parra-Martinez, Alba; Yang, Rui; Haljasmagi, Liis; Migaud, Melanie; Sarekannu, 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; Garcon, Pierre; Riviere, Jacques G.; Lagier, Jean-Christophe; Gentile, Stephanie; 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.; Franco, Jose Luis; Anaya, Juan-Manuel; Sole-Violan, Jordi; Imberti, Luisa; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Delmonte, Ottavia M.; Zhang, Yu; Snow, Andrew L.; Holland, Steven M.; Biggs, Catherine M.; Moncada-Velez, Marcela; Arias, Andres 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; Ramirez-Santana, Carolina; Paul, Stephane; Pan-Hammarstrom, Qiang; Hammarstrom, Lennart; Dupont, Annabelle; Kurolap, Alina; Metz, Christine N.; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Ciceri, Fabio; Barreiros, Lucila A.; Dominguez-Garrido, Elena; Vidigal, Mateus; Zatz, Mayana; van, de Beek Diederik; Sahanic, Sabina; Tancevski, Ivan; Stepanovskyy, Yurii; Boyarchuk, Oksana; Nukui, Yoko; Tsumura, Miyuki; Vidaur, Loreto; Tangye, Stuart G.; Burrel, Sonia; Duffy, Darragh; Quintana-Murci, Lluis; Klocperk, Adam; Kann, Nelli Y.; Shcherbina, Anna; Lau, Yu-Lung; Leung, Daniel; Coulongeat, Matthieu; Marlet, Julien; Koning, Rutger; Reyes, Luis Felipe; Chauvineau-Grenier, Angelique; Venet, Fabienne; Monneret, Guillaume; Nussenzweig, Michel C.; Arrestier, Romain; Boudhabhay, Idris; Baris-Feldman, Hagit; Hagin, David; Wauters, Joost; Meyts, Isabelle; Dyer, Adam H.; Kennelly, Sean P.; Bourke, Nollaig M.; Halwani, Rabih; Sharif-Askari, Narjes Saheb; Dorgham, Karim; Sallette, Jerome; Sedkaoui, Souad Mehlal; AlKhater, Suzan; Rigo-Bonnin, Raul; Morandeira, Francisco; Roussel, Lucie; Vinh, Donald C.; Ostrowski, Sisse Rye; Condino-Neto, Antonio; Prando, Carolina; Bondarenko, Anastasiia; Spaan, Andras N.; Gilardin, Laurent; Fellay, Jacques; Lyonnet, Stanislas; Bilguvar, Kaya; Lifton, Richard P.; Mane, Shrikant; Anderson, Mark S.; Boisson, Bertrand; Beziat, Vivien; Zhang, Shen-Ying; Andreakos, Evangelos; Hermine, Olivier; Pujol, Aurora; Peterson, Part; Mogensen, Trine H.; Rowen, Lee; Mond, James; Debette, Stephanie; de, Lamballerie Xavier; Duval, Xavier; Mentre, France; Zins, Marie; Soler-Palacin, Pere; Colobran, Roger; Gorochov, Guy; Solanich, Xavier; Susen, Sophie; Martinez-Picado, Javier; Raoult, Didier; Vasse, Marc; Gregersen, Peter K.; Piemonti, Lorenzo; Rodriguez-Gallego, Carlos; Notarangelo, Luigi D.; Su, Helen C.; Kisand, Kai; Okada, Satoshi; Puel, Anne; Jouanguy, Emmanuelle; Rice, Charles M.; Tiberghien, Pierre; Zhang, Qian; Cobat, Aurelie; Abel, Laurent; Casanova, Jean-Laurent ✉; Maródi, L [Maródi, László (Klinikai immunoló...), Kollaborációs közreműködő] Bőr-,
Nemikórtani és Bőronkológiai Klinika (SE / AOK / K); HGID Lab COVID Clinicians COVID-STORM Clinicians NIAID Immune Response Covid Grp NH-COVAIR
Study Grp Danish CHGE Danish Blood Donor Study St Jamess Hosp Sars CoV2 Interest French
COVID Cohort Study Grp Imagine COVID-Grp Milieu Interieur Consortium CoV-Contact Cohort
Amsterdam Umc Covid-19 Biobank Inv COVID Human Genetic Efft CONSTANCES Cohort 3C-Dijon
Study Cerba HealthCare Etab Sang Study Grp [Kollaborációs szervezet]
Angol nyelvű Sokszerzős vagy csoportos szerzőségű szakcikk (Folyóiratcikk) Tudományos
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml;
in plasma diluted 1:10) of IFN-alpha and/or IFN-omega 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-alpha and/or IFN-omega (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-beta.
We also show, in a sample of 34,159 uninfected individuals from the general population,
that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega 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-beta 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.
