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Human genetic and immunological determinants of critical COVID-19 pneumonia

2022; Nature Portfolio; Volume: 603; Issue: 7902 Linguagem: Inglês

10.1038/s41586-022-04447-0

1476-4687

Qian Zhang, Paul Bastard, Adem Karbuz, Adrian Gervais, Ahmad Abou Tayoun, Alessandro Aiuti, Alexandre Bélot, Alexandre Bolze, Alexandre Gaudet, Анастасія Бондаренко, Zhiyong Liu, András N. Spaan, Andrea Guennoun, Andrés A. Arias, Anna M. Planas, Anna Šedivá, Anna Shcherbina, Anna‐Lena Neehus, Anne Puel, Antoine Froidure, Antonio Novelli, Aslınur Özkaya Parlakay, Aurora Pujol, Aysun Yahşi, Belgi̇n Gülhan, Benedetta Bigio, Bertrand Boisson, Beth A. Drolet, Carlos A. Arango-Franco, Carlos Flores, Carlos Rodríguez‐Gallego, Carolina Prando, Catherine M. Biggs, Charles‐Édouard Luyt, Clifton L. Dalgard, Cliona OʼFarrelly, Daniela Matuozzo, David Dalmau, David S. Perlin, Davood Mansouri, Diederik van de Beek, Donald C. Vinh, Elena Domínguez‐Garrido, Elena W.Y. Hsieh, Emine Hafize Erdeniz, Emmanuelle Jouanguy, Esra Şevketoğlu, Estelle Talouarn, Eugenia Quirós-Roldán, Evangelos Andreakos, Eystein S. Husebye, Fahad Alsohime, Filomeen Haerynck, Giorgio Casari, Giuseppe Novelli, Gökhan Aytekіn, Guillaume Morelle, Gülsüm Alkan, Gülsüm İclal Bayhan, Hagit Baris Feldman, Helen C. Su, Horst von Bernuth, Igor Resnick, Ingrid G. Bustos, Isabelle Meyts, Isabelle Migeotte, Ivan Tancevski, Jacinta Bustamante, Jacques Fellay, Jamila El Baghdadi, Javier Martínez‐Picado, Jean‐Laurent Casanova, Jérémie Rosain, Jérémy Manry, Jie Chen, John Christodoulou, Jonathan Bohlen, José Luis Franco, Juan Li, Juan‐Manuel Anaya, Julián Rojas, YE Junqiang, K. M. Furkan Uddin, Kadriye Kart Yaşar, Kai Kisand, Keisuke Okamoto, Khalil Chaïbi, Kristina Mironska, László Maródi, Laurent Abel, Laurent Rénia, Lazaro Lorenzo, Lennart Hammarström, Lisa F. P. Ng, Lluís Quintana‐Murci, Lucía Victoria Erazo-Borrás, Luigi D. Notarangelo, Luis Felipe Reyes, Luís M. Allende, Luisa Imberti, Majistor Raj Luxman Maglorius Renkilaraj, Marcela Moncada‐Vélez, Marie Materna, Mark S. Anderson, Marta Gut, Marwa Chbihi, Masato Ogishi, Melike Emiroğlu, Mikko Seppänen, Mohammed Uddin, Mohammed Shahrooei, N. Larcombe Alexander, Nevin Hatipoğlu, Nico Marr, Nihal Akçay, Oksana Boyarchuk, Ondřej Slabý, Özge Metin Akcan, Peng Zhang, Pere Soler‐Palacín, Peter K. Gregersen, Petter Brodin, Pierre Garçon, Pierre‐Emmanuel Morange, Qiang Pan‐Hammarström, Qinhua Zhou, Quentin Philippot, Rabih Halwani, Rebeca Pérez de Diego, Romain Lévy, Rui Yang, Şadiye Kübra Tüter Öz, Saleh Al Muhsen, Saliha Kanık Yüksek, Sara Elva Espinosa‐Padilla, Sathishkumar Ramaswamy, Satoshi Okada, Şefika Elmas Bozdemir, Selma Erol Aytekin, Şemsi Nur Karabela, Sevgi Keleş, Sevtap Şenoğlu, Shen‐Ying Zhang, Sotiriјa Duvlis, Stefan N. Constantinescu, Stéphanie Boisson‐Dupuis, Stuart E. Turvey, Stuart G. Tangye, Takaki Asano, Tayfun Özçelık, Tom Le Voyer, Tom Maniatis, Tomohiro Morio, Trine H. Mogensen, Vanessa Sancho‐Shimizu, Vivien Béziat, Xavier Solanich, Yenan T. Bryceson, YL Lau, Yuval Itan, Aurélie Cobat, Jean‐Laurent Casanova,

SARS-CoV-2 and COVID-19 Research

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 IFNα, IFNβ and/or IFNω, 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. The COVID Human Genetic Effort examines the molecular, cellular and immunological determinants of the various SARS-CoV-2-related disease manifestations by searching for causal errors of immunity.