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

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-...

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Autores principales: Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Bilguvar, Kaya, Ye, Junqiang, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Onodi, Fanny, Korniotis, Sarantis, Karpf, Léa, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M., Razooky, Brandon S., Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Ji Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Seeleuthner, Yoann, Manry, Jeremy, Masson, Cecile, Schmitt, Yohann, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F., Mansouri, Davood, Al-Saud, Haya, Al-Mulla, Fahd, Almourfi, Feras, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, van de Beek, Diederik, Biondi, Andrea, Bettini, Laura Rachele, D’Angio’, Mariella, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Oler, Andrew J., Tompkins, Miranda F., Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Smits, Guillaume, Migeotte, Isabelle, Haerynck, Filomeen, Soler-Palacin, Pere, Martin-Nalda, Andrea, Colobran, Roger, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Hraiech, Sami, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Laouénan, Cédric, Snow, Andrew L., Dalgard, Clifton L., Milner, Joshua D., Vinh, Donald C., Mogensen, Trine H., Marr, Nico, Spaan, András N., Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Puel, Anne, Ciancanelli, Michael J., Meyts, Isabelle, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Nussenzweig, Michel, García-Sastre, Adolfo, Krammer, Florian, Pujol, Aurora, Duffy, Darragh, Lifton, Richard P., Zhang, Shen-Ying, Gorochov, Guy, Béziat, Vivien, Jouanguy, Emmanuelle, Sancho-Shimizu, Vanessa, Rice, Charles M., Abel, Laurent, Notarangelo, Luigi D., Cobat, Aurélie, Su, Helen C., Casanova, Jean-Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857407/
https://www.ncbi.nlm.nih.gov/pubmed/32972995
http://dx.doi.org/10.1126/science.abd4570
Descripción
Sumario: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.

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