Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
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Zhang, Qian | Bastard, Paul | Liu, Zhiyong | Le Pen, Jérémie | Moncada-Velez, Marcela | Chen, Jie | Ogishi, Masato | Sabli, Ira | 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 | Razooky, Brandon | 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 | 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 | Tompkins, Miranda | 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 | Gallego, Carlos Rodríguez | Novelli, Giuseppe | Hraiech, Sami | Tandjaoui-Lambiotte, Yacine | Duval, Xavier | Laouénan, Cédric | Tual, Christelle | Snow, Andrew | Dalgard, Clifton | Milner, Joshua | Vinh, Donald | Mogensen, Trine | Marr, Nico | Spaan, András | Boisson, Bertrand | Boisson-Dupuis, Stéphanie | Bustamante, Jacinta | Puel, Anne | Ciancanelli, Michael | Meyts, Isabelle | Maniatis, Tom | Soumelis, Vassili | Amara, Ali | Nussenzweig, Michel | García-Sastre, Adolfo | Krammer, Florian | Pujol, Aurora | Duffy, Darragh | Lifton, Richard | Zhang, Shen-Ying | Gorochov, Guy | Béziat, Vivien | Jouanguy, Emmanuelle | Sancho-Shimizu, Vanessa | Rice, Charles | Abel, Laurent | Notarangelo, Luigi | Richard, Jean-Christophe | Cobat, Aurélie | Su, Helen | Casanova, Jean-Laurent | van Der Werf, Sylvie
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CCSD ; American Association for the Advancement of Science (AAAS) -
International audience.
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.
