@article{Zhang_Q-2020_216789,
title = {Inborn errors of type I IFN immunity in patients with life-threatening COVID-19},
author = {Zhang, Q. and Bastard, P. and Liu, Z. and Le Pen, J. and Moncada-Velez, M. and Chen, J. and Ogishi, M. and Sabli, I. and Hodeib, S. and Korol, C. and Rosain, J. and Bilguvar, K. and Ye, J. and Bolze, A. and Bigio, B. and Yang, R. and Arias, A. and Zhou, Q. and Zhang, Y. and Onodi, F. and Korniotis, S. and Karpf, L. and Philippot, Q. and Chbihi, M. and Bonnet-Madin, L. and Dorgham, K. and Smith, N. and Schneider, W. and Razooky, B. and Hoffmann, H. and Michailidis, E. and Moens, L. and Han, J. and Lorenzo, L. and Bizien, L. and Meade, P. and Neehus, A. and Ugurbil, A. and Corneau, A. and Kerner, G. and Zhang, P. and Rapaport, F. and Seeleuthner, Y. and Manry, J. and Masson, C. and Schmitt, Y. and Schlüter, A. and Le Voyer, T. and Khan, T. and Li, J. and Fellay, J. and Roussel, L. and Shahrooei, M. and Alosaimi, M. and Mansouri, D. and Al-Saud, H. and Al-Mulla, F. and Almourfi, F. and Al-Muhsen, S. and Alsohime, F. and Al Turki, S. and Hasanato, R. and van de Beek, D. and Biondi, A. and Bettini, L. and D’Angio’, M. and Bonfanti, P. and Imberti, L. and Sottini, A. and Paghera, S. and Quiros-Roldan, E. and Rossi, C. and Oler, A. and Tompkins, M. and Alba, C. and Vandernoot, I. and Goffard, J. and Smits, G. and Migeotte, I. and Haerynck, F. and Soler-Palacín, P. and Martin-Nalda, A. and Colobran, R. and Morange, P. and Keles, S. and Çölkesen, F. and Özçelik, T. and Yasar, K. and Senoglu, S. and Karabela, Ş. and Rodriguez-Gallego, C. and Novelli, G. and Hraiech, S. and Tandjaoui-Lambiotte, Y. and Duval, X. and Laouénan, C. and Snow, A. and Dalgard, C. and Milner, J. and Vinh, D. and Mogensen, T. and Marr, N. and Spaan, A. and Boisson, B. and Boisson-Dupuis, S. and Bustamante, J. and Puel, A. and Ciancanelli, M. and Meyts, I. and Maniatis, T. and Soumelis, V. and Amara, A. and Nussenzweig, M. and García-Sastre, A. and Krammer, F. and Pujol, A. and Duffy, D. and Lifton, R. and Zhang, S. and Gorochov, G. and Béziat, V. and Jouanguy, E. and Sancho-Shimizu, V. and Rice, C. and Abel, L. and Notarangelo, L. and Cobat, A. and Su, H. and Casanova, J.},
month = {oct},
year = {2020},
abstract = {Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.},
volume = {370},
issue = {6515},
journal = {Science},
publisher = {American Association for the Advancement of Science},
url = {https://doi.org/10.1126/science.abd4570},
}
