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

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.

• Autores: Arias Sierra, Andrés Augusto; Moncada Vélez, Marcela; Zhang, Qian; Bastard, Paul; Liu, Zhiyong; Le Pen, Jérémie; Chen, Jie; Ogishi, Masato; Sabli, Ira K D; Hodeib, Stephanie; Korol, Cecilia; Vandernoot, Isabelle; Goffard, Jean Christophe; Smits, Guillaume; Migeotte, Isabelle; Haerynck, Filomeen; Soler Palacin, Pere; Martin Nalda, Andrea; Colobran, Roger; Morange, Pierre Emmanuel; Keles, Sevgi; Puel, Anne; Çölkesen, Fatma; Ozcelik, Tayfun; Kart Yasar, Kadriye; Senoglu, Sevtap; Karabela, Şemsi Nur; Rodríguez Gallego, Carlos; Novelli, Giuseppe; Hraiech, Sami; Tandjaoui-Lambiotte, Yacine; Duval, Xavier; Ciancanelli, Michael J.; Laouénan, Cédric; Spaan, András N.; Boisson, Bertrand; Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; Maniatis, Tom; Soumelis, Vassili; Amara, Ali; Nussenzweig, Michel; Notarangelo, Luigi D.; Su, Helen C.; Cobat, Aurélie; Gorochov, Guy; Rosain, Jérémie; Béziat, Vivien; Jouanguy, Emmanuelle; Meyts, Isabelle; García-Sastre, Adolfo; Krammer, Florian; Pujol, Aurora; Duffy, Darragh; Marr, Nico; Lifton, Richard P; Zhang, Shen-Ying; Bilguvar, Kaya; Rice, Charles M.; Abel, Laurent; Béziat, Vivien; Sancho Shimizu, Vanessa; Casanova, Jean Laurent; Ye, Junqiang; Bolze, Alexandre; Bigio, Benedetta; Yang, Rui; 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, Mohammad 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
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40727
• Acceso en línea: https://hdl.handle.net/10495/40727
• Palabra clave: Alleles; Alelos; Asymptomatic Infections; Infecciones Asintomáticas; Betacoronavirus; COVID-19; Coronavirus Infections; Infecciones por Coronavirus; Genetic Loci; Sitios Genéticos; Genetic Predisposition to Disease; Predisposición Genética a la Enfermedad; Interferon Regulatory Factor-7; Factor 7 Regulador del Interferón; Loss of Function Mutation; Mutación con Pérdida de Función; Pneumonia, Viral; Neumonía Viral; Receptor, Interferon alpha-beta; Receptor de Interferón alfa y beta; SARS-CoV-2; SARS-CoV-2; Toll-Like Receptor 3; Receptor Toll-Like 3; https://id.nlm.nih.gov/mesh/D000483; https://id.nlm.nih.gov/mesh/D058345; https://id.nlm.nih.gov/mesh/D000073640; https://id.nlm.nih.gov/mesh/D000086382; https://id.nlm.nih.gov/mesh/D018352; https://id.nlm.nih.gov/mesh/D056426; https://id.nlm.nih.gov/mesh/D020022; https://id.nlm.nih.gov/mesh/D050839; https://id.nlm.nih.gov/mesh/D000073658; https://id.nlm.nih.gov/mesh/D011024; https://id.nlm.nih.gov/mesh/D053633; https://id.nlm.nih.gov/mesh/D000086402; https://id.nlm.nih.gov/mesh/D051196
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/