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

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      Author(s)
      Manry, J.
      Bastard, P.
      Gervais, A.
      Le Voyer, T.
      Rosain, J.
      Philippot, Q.
      Michailidis, E.
      Hoffmann, H.
      Eto, S.
      Garcia-Prat, M.
      Bizien, L.
      Parra-Martínez, A.
      Yang, R.
      Haljasmägi, L.
      Migaud, M.
      Särekannu, 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.
      Garçpn, P.
      Rivière, J. G.
      Lagier, J.
      Gentile, S.
      Rosen, L. B.
      Shaw, E.
      Morio, T.
      Tanaka, J.
      Dalmau, D.
      Tharaux, P.
      Sene, D.
      Stepanian, A.
      Mégarbane, B.
      Triantafyllia, V.
      Fekkar, A.
      Heath, J. R.
      Franco, J. L.
      Anaya, J.
      Solé-Violán, J.
      Imberti, L.
      Biondi, A.
      Bonfanti, P.
      Castagnoli, R.
      Delmonte, O. M.
      Zhang, Y.
      Snow, A. L.
      Holland, S. M.
      Biggs, C. M.
      Moncada-Vélez, M.
      Arias, A. A.
      Lorenzo, L.
      Boucherit, S.
      Anglicheau, D.
      Planas, A. M.
      Haerynck, F.
      Duvlis, S.
      Ozcelik, Tayfun
      Keles, S.
      Bousfiha, A. A.
      El Bakkouri, J.
      Ramirez-Santana, C.
      Paul, S.
      Pan-Hammarström, Q.
      Hammarström, L.
      Dupont, A.
      Kurolap, A.
      Metz, C. N.
      Aiuti, A.
      Casari, G.
      Lampasona, V.
      Ciceri, F.
      Barreiros, L. A.
      Dominguez-Garrido, E.
      Vidigal, M.
      Zatz, M.
      van de Beek, D.
      Sahanic, S.
      Tancevski, I.
      Stepanovskyy, Y.
      Boyarchuk, O.
      Nukui, Y.
      Tsumura, M.
      Vidaur, L.
      Tangye, S. G.
      Burrel, S.
      Duffy, D.
      Quintana-Murci, L.
      Klocperk, A.
      Kann, N. Y.
      Shcherbina, A.
      Lau, Y.
      Leung, D.
      Coulongeat, M.
      Marlet, J.
      Koning, R.
      Reyes, L. F.
      Chauvineau-Grenier, A.
      Venet, F.
      Monneret, G.
      Nussenzweig, M. C.
      Arrestier, R.
      Boudhabhay, I.
      Baris-Feldman, H.
      Hagin, D.
      Wauters, J.
      Meyts, I.
      Dyer, A. H.
      Kennelly, S. P.
      Bourke, N. M.
      Halwani, R.
      Sharif-Askari, F. S.
      Dorgham, K.
      Sallette, J.
      Sedkaoui, S. M.
      AlKhater, S.
      Rigo-Bonnin, R.
      Morandeira, F.
      Roussel, L.
      Vinh, D. C.
      Erikstrup, C.
      Condino-Neto, A.
      Prando, C.
      Bondarenko, A.
      Spaan, A. N.
      Gilardin, L.
      Fellay, J.
      Lyonnet, S.
      Bilguvar, K.
      Lifton, R. P.
      Mane, S.
      Anderson, M. S.
      Boisson, B.
      Béziat, V.
      Zhang, S.
      Andreakos, E.
      Hermine, O.
      Pujol, A.
      Peterson, P.
      Mogensen, T. H.
      Rowen, L.
      Mond, J.
      Debette, S.
      de Lamballerie, X.
      Burdet, C.
      Bouadma, L.
      Zins, M.
      Soler-Palacin, P.
      Colobran, R.
      Gorochov, G.
      Solanich, X.
      Susen, S.
      Martinez-Picado, J.
      Raoult, D.
      Vasse, M.
      Gregersen, P. K.
      Piemonti, L.
      Rodríguez-Gallego, C.
      Notarangelo, L. D.
      Su, H. C.
      Kisand, K.
      Okada, S.
      Puel, A.
      Jouanguy, E.
      Rice, C. M.
      Tiberghien, P.
      Zhang, Q.
      Casanova, J.
      Abel, L.
      Cobat, A.
      Date
      2022-05-16
      Source Title
      Proceedings of the National Academy of Sciences of the United States of America
      Print ISSN
      0027-8424
      Electronic ISSN
      1091-6490
      Publisher
      National Academy of Sciences
      Volume
      119
      Issue
      21
      Language
      English
      Type
      Article
      Item Usage Stats
      28
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      108
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      Abstract
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y 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, and in ∼1% of individuals aged [removed]4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
      Keywords
      COVID-19
      Type I IFNs
      Autoantibodies
      Relative risk
      Infection fatality rate
      Permalink
      http://hdl.handle.net/11693/111766
      Published Version (Please cite this version)
      https://dx.doi.org/10.1073/pnas.2200413119
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