1. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
- Author
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Zhang, Q, Liu, Z, Moncada-Velez, M, Chen, J, Ogishi, M, Bigio, B, Yang, R, Arias, AA, Zhou, Q, Han, JE, Ugurbil, AC, Zhang, P, Rapaport, F, Li, J, Spaan, AN, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, MJ, Zhang, SY, Béziat, V, Jouanguy, E, Abel, L, Cobat, A, Casanova, JL, Bastard, P, Korol, C, Rosain, J, Philippot, Q, Chbihi, M, Lorenzo, L, Bizien, L, Neehus, AL, Kerner, G, Seeleuthner, Y, Manry, J, Le Voyer, T, Le Pen, J, Schneider, WM, Razooky, BS, Hoffmann, HH, Michailidis, E, Rice, CM, Sabli, IKD, Hodeib, S, Sancho-Shimizu, V, Bilguvar, K, Ye, J, Maniatis, T, Bolze, A, Zhang, Y, Notarangelo, LD, Su, HC, Onodi, F, Korniotis, S, Karpf, L, Soumelis, V, Bonnet-Madin, L, Amara, A, Dorgham, K, Gorochov, G, Smith, N, Duffy, D, Moens, L, Meyts, I, Zhang, Q, Liu, Z, Moncada-Velez, M, Chen, J, Ogishi, M, Bigio, B, Yang, R, Arias, AA, Zhou, Q, Han, JE, Ugurbil, AC, Zhang, P, Rapaport, F, Li, J, Spaan, AN, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, MJ, Zhang, SY, Béziat, V, Jouanguy, E, Abel, L, Cobat, A, Casanova, JL, Bastard, P, Korol, C, Rosain, J, Philippot, Q, Chbihi, M, Lorenzo, L, Bizien, L, Neehus, AL, Kerner, G, Seeleuthner, Y, Manry, J, Le Voyer, T, Le Pen, J, Schneider, WM, Razooky, BS, Hoffmann, HH, Michailidis, E, Rice, CM, Sabli, IKD, Hodeib, S, Sancho-Shimizu, V, Bilguvar, K, Ye, J, Maniatis, T, Bolze, A, Zhang, Y, Notarangelo, LD, Su, HC, Onodi, F, Korniotis, S, Karpf, L, Soumelis, V, Bonnet-Madin, L, Amara, A, Dorgham, K, Gorochov, G, Smith, N, Duffy, D, Moens, L, and Meyts, I
- 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.
- Published
- 2020