Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal 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 TLR3- and 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 define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway 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.

Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., et al. (2020). Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. SCIENCE, 370(6515) [10.1126/science.abd4570].

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Biondi, Andrea;Bettini, Laura Rachele;D'Angio, Mariella;Bonfanti, Paolo;Pesci, Alberto
Membro del Collaboration Group
2020

Abstract

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal 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 TLR3- and 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 define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway 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.
Articolo in rivista - Articolo scientifico
COVID19
English
Pesci, Alberto COVID-STORM Clinicians
Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., et al. (2020). Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. SCIENCE, 370(6515) [10.1126/science.abd4570].
Zhang, Q; Bastard, P; Liu, Z; Le Pen, J; Moncada-Velez, M; Chen, J; Ogishi, M; Sabli, I; Hodeib, S; Korol, C; Rosain, J; Bilguvar, K; Ye, J; Bolze, A; Bigio, B; Yang, R; Arias, A; Zhou, Q; Zhang, Y; Onodi, F; Korniotis, S; Karpf, L; Philippot, Q; Chbihi, M; Bonnet-Madin, L; Dorgham, K; Smith, N; Schneider, W; Razooky, B; Hoffmann, H; Michailidis, E; Moens, L; Han, J; Lorenzo, L; Bizien, L; Meade, P; Neehus, A; Ugurbil, A; Corneau, A; Kerner, G; Zhang, P; Rapaport, F; Seeleuthner, Y; Manry, J; Masson, C; Schmitt, Y; Schlüter, A; Le Voyer, T; Khan, T; Li, J; Fellay, J; Roussel, L; Shahrooei, M; Alosaimi, M; Mansouri, D; Al-Saud, H; Al-Mulla, F; Almourfi, F; Al-Muhsen, S; Alsohime, F; Al Turki, S; Hasanato, R; van de Beek, D; Biondi, A; Bettini, L; D'Angio, M; Bonfanti, P; Imberti, L; Sottini, A; Paghera, S; Quiros-Roldan, E; Rossi, C; Oler, A; Tompkins, M; Alba, C; Vandernoot, I; Goffard, J; Smits, G; Migeotte, I; Haerynck, F; Soler-Palacin, P; Martin-Nalda, A; Colobran, R; Morange, P; Keles, S; Çölkesen, F; Ozcelik, T; Yasar, K; Senoglu, S; Karabela, Ş; Gallego, C; Novelli, G; Hraiech, S; Tandjaoui-Lambiotte, Y; Duval, X; Laouénan, C; Snow, A; Dalgard, C; Milner, J; Vinh, D; Mogensen, T; Marr, N; Spaan, A; Boisson, B; Boisson-Dupuis, S; Bustamante, J; Puel, A; Ciancanelli, M; Meyts, I; Maniatis, T; Soumelis, V; Amara, A; Nussenzweig, M; García-Sastre, A; Krammer, F; Pujol, A; Duffy, D; Lifton, R; Zhang, S; Gorochov, G; Béziat, V; Jouanguy, E; Sancho-Shimizu, V; Rice, C; Abel, L; Notarangelo, L; Cobat, A; Su, H; Casanova, J; Pesci, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/285978
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