@article{8752786,
  abstract     = {{SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFN alpha, IFN beta and/or IFN omega, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.}},
  author       = {{Zhang, Qian and Bastard, Paul and Karbuz, Adem and Gervais, Adrian and Tayoun, Ahmad Abou and Aiuti, Alessandro and Belot, Alexandre and Bolze, Alexandre and Gaudet, Alexandre and Bondarenko, Anastasiia and Liu, Zhiyong and Spaan, András N. and Guennoun, Andrea and Arias, Andres Augusto and Planas, Anna M. and Sediva, Anna and Shcherbina, Anna and Neehus, Anna-Lena and Puel, Anne and Froidure, Antoine and Novelli, Antonio and Parlakay, Aslınur Özkaya and Pujol, Aurora and Yahşi, Aysun and Gülhan, Belgin and Bigio, Benedetta and Boisson, Bertrand and Drolet, Beth A. and Franco, Carlos Andres Arango and Flores, Carlos and Rodríguez-Gallego, Carlos and Prando, Carolina and Biggs, Catherine M. and Luyt, Charles-Edouard and Dalgard, Clifton L. and O’Farrelly, Cliona and Matuozzo, Daniela and Dalmau, David and Perlin, David S. and Mansouri, Davood and van de Beek, Diederik and Vinh, Donald C. and Dominguez-Garrido, Elena and Hsieh, Elena W. Y. and Erdeniz, Emine Hafize and Jouanguy, Emmanuelle and Şevketoglu, Esra and Talouarn, Estelle and Quiros-Roldan, Eugenia and Andreakos, Evangelos and Husebye, Eystein and Alsohime, Fahad and Haerynck, Filomeen and Casari, Giorgio and Novelli, Giuseppe and Aytekin, Gökhan and Morelle, Guillaume and Alkan, Gulsum and Bayhan, Gulsum Iclal and Feldman, Hagit Baris and Su, Helen C. and von Bernuth, Horst and Resnick, Igor and Bustos, Ingrid and Meyts, Isabelle and Migeotte, Isabelle and Tancevski, Ivan and Bustamante, Jacinta and Fellay, Jacques and El Baghdadi, Jamila and Martinez-Picado, Javier and Casanova, Jean-Laurent and Rosain, Jeremie and Manry, Jeremy and Chen, Jie and Christodoulou, John and Bohlen, Jonathan and Franco, José Luis and Li, Juan and Anaya, Juan Manuel and Rojas, Julian and Ye, Junqiang and Uddin, K. M. Furkan and Yasar, Kadriye Kart and Kisand, Kai and Okamoto, Keisuke and Chaïbi, Khalil and Mironska, Kristina and Maródi, László and Abel, Laurent and Renia, Laurent and Lorenzo, Lazaro and Hammarström, Lennart and Ng, Lisa F. P. and Quintana-Murci, Lluis and Erazo, Lucia Victoria and Notarangelo, Luigi D. and Reyes, Luis Felipe and Allende, Luis M. and Imberti, Luisa and Renkilaraj, Majistor Raj Luxman Maglorius and Moncada-Velez, Marcela and Materna, Marie and Anderson, Mark S. and Gut, Marta and Chbihi, Marwa and Ogishi, Masato and Emiroglu, Melike and Seppänen, Mikko R. J. and Uddin, Mohammed J. and Shahrooei, Mohammed and Alexander, Natalie and Hatipoglu, Nevin and Marr, Nico and Akçay, Nihal and Boyarchuk, Oksana and Slaby, Ondrej and Akcan, Ozge Metin and Zhang, Peng and Soler-Palacín, Pere and Gregersen, Peter K. and Brodin, Petter and Garçon, Pierre and Morange, Pierre-Emmanuel and Pan-Hammarström, Qiang and Zhou, Qinhua and Philippot, Quentin and Halwani, Rabih and de Diego, Rebeca Perez and Levy, Romain and Yang, Rui and Öz, Şadiye Kübra Tüter and Muhsen, Saleh Al and Kanık-Yüksek, Saliha and Espinosa-Padilla, Sara and Ramaswamy, Sathishkumar and Okada, Satoshi and Bozdemir, Sefika Elmas and Aytekin, Selma Erol and Karabela, Şemsi Nur and Keles, Sevgi and Senoglu, Sevtap and Zhang, Shen-Ying and Duvlis, Sotirija and Constantinescu, Stefan N. and Boisson-Dupuis, Stephanie and Turvey, Stuart E. and Tangye, Stuart G. and Asano, Takaki and Ozcelik, Tayfun and Le Voyer, Tom and Maniatis, Tom and Morio, Tomohiro and Mogensen, Trine H. and Sancho-Shimizu, Vanessa and Beziat, Vivien and Solanich, Xavier and Bryceson, Yenan and Lau, Yu-Lung and Itan, Yuval and Cobat, Aurélie and Casanova, Jean-Laurent and COVID Human Genetic Effort, [missing]}},
  issn         = {{0028-0836}},
  journal      = {{NATURE}},
  keywords     = {{Multidisciplinary,PLASMACYTOID DENDRITIC CELLS,CHRONIC MUCOCUTANEOUS CANDIDIASIS,MYASTHENIA-GRAVIS PATIENTS,SINGLE-STRANDED RNA,SARS-COV-2 INFECTION,PROTECTIVE IMMUNITY,DISTINCT FUNCTIONS,INBORN-ERRORS,HIGH BURDEN,INTERFERON}},
  language     = {{eng}},
  number       = {{7902}},
  pages        = {{587--598}},
  title        = {{Human genetic and immunological determinants of critical COVID-19 pneumonia}},
  url          = {{http://doi.org/10.1038/s41586-022-04447-0}},
  volume       = {{603}},
  year         = {{2022}},
}

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