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      Human genetic and immunological determinants of critical COVID-19 pneumonia

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      Author(s)
      Zhang, Qian
      Bastard, Paul
      Karbuz, Adem
      Gervais, Adrian
      Tayoun, Ahmad Abou
      Aiuti, Alessandro
      Belot, Alexandre
      Bolze, Alexandre
      Gaudet, Alexandre
      Bondarenko, Anastasiia
      Liu, Zhiyong
      Spaan, András N.
      Guennoun, Andrea
      Arias, Andres Augusto
      Planas, Anna M.
      Sediva, Anna
      Shcherbina, Anna
      Neehus, Anna-Lena
      Puel, Anne
      Froidure, Antoine
      Novelli, Antonio
      Parlakay, Aslınur Özkaya
      Pujol, Aurora
      Yahşi, Aysun
      Gülhan, Belgin
      Bigio, Benedetta
      Boisson, Bertrand
      Drolet, Beth A.
      Franco, Carlos Andres Arango
      Flores, Carlos
      Rodríguez-Gallego, Carlos
      Prando, Carolina
      Biggs, Catherine M.
      Luyt, Charles-Edouard
      Dalgard, Clifton L.
      O’Farrelly, Cliona
      Matuozzo, Daniela
      Dalmau, David
      Perlin, David S.
      Mansouri, Davood
      van de Beek, Diederik
      Vinh, Donald C.
      Dominguez-Garrido, Elena
      Hsieh, Elena W. Y.
      Erdeniz, Emine Hafize
      Jouanguy, Emmanuelle
      Şevketoglu, Esra
      Talouarn, Estelle
      Quiros-Roldan, Eugenia
      Andreakos, Evangelos
      Husebye, Eystein
      Alsohime, Fahad
      Haerynck, Filomeen
      Casari, Giorgio
      Novelli, Giuseppe
      Aytekin, Gökhan
      Morelle, Guillaume
      Alkan, Gulsum
      Bayhan, Gulsum Iclal
      Feldman, Hagit Baris
      Su, Helen C.
      von Bernuth, Horst
      Resnick, Igor
      Bustos, Ingrid
      Meyts, Isabelle
      Migeotte, Isabelle
      Tancevski, Ivan
      Bustamante, Jacinta
      Fellay, Jacques
      El Baghdadi, Jamila
      Martinez-Picado, Javier
      Casanova, Jean-Laurent
      Rosain, Jeremie
      Manry, Jeremy
      Chen, Jie
      Christodoulou, John
      Bohlen, Jonathan
      Franco, José Luis
      Li, Juan
      Anaya, Juan Manuel
      Rojas, Julian
      Ye, Junqiang
      Uddin, K. M. Furkan
      Yasar, Kadriye Kart
      Kisand, Kai
      Okamoto, Keisuke
      Chaïbi, Khalil
      Mironska, Kristina
      Maródi, László
      Abel, Laurent
      Renia, Laurent
      Lorenzo, Lazaro
      Hammarström, Lennart
      Ng, Lisa F. P.
      Quintana-Murci, Lluis
      Erazo, Lucia Victoria
      Notarangelo, Luigi D.
      Reyes, Luis Felipe
      Allende, Luis M.
      Imberti, Luisa
      Renkilaraj, Majistor Raj Luxman Maglorius
      Moncada-Velez, Marcela
      Materna, Marie
      Anderson, Mark S.
      Gut, Marta
      Chbihi, Marwa
      Ogishi, Masato
      Emiroglu, Melike
      Seppänen, Mikko R. J.
      Uddin, Mohammed J.
      Shahrooei, Mohammed
      Alexander, Natalie
      Hatipoglu, Nevin
      Marr, Nico
      Akçay, Nihal
      Boyarchuk, Oksana
      Slaby, Ondrej
      Akcan, Ozge Metin
      Zhang, Peng
      Soler-Palacín, Pere
      Gregersen, Peter K.
      Brodin, Petter
      Garçon, Pierre
      Morange, Pierre-Emmanuel
      Pan-Hammarström, Qiang
      Zhou, Qinhua
      Philippot, Quentin
      Halwani, Rabih
      de Diego, Rebeca Perez
      Levy, Romain
      Yang, Rui
      Öz, Şadiye Kübra Tüter
      Muhsen, Saleh Al
      Kanık-Yüksek, Saliha
      Espinosa-Padilla, Sara
      Ramaswamy, Sathishkumar
      Okada, Satoshi
      Bozdemir, Sefika Elmas
      Aytekin, Selma Erol
      Karabela, Şemsi Nur
      Keles, Sevgi
      Senoglu, Sevtap
      Zhang, Shen-Ying
      Duvlis, Sotirija
      Constantinescu, Stefan N.
      Boisson-Dupuis, Stephanie
      Turvey, Stuart E.
      Tangye, Stuart G.
      Asano, Takaki
      Özcelik, Tayfun
      Le Voyer, Tom
      Maniatis, Tom
      Morio, Tomohiro
      Mogensen, Trine H.
      Sancho-Shimizu, Vanessa
      Beziat, Vivien
      Solanich, Xavier
      Bryceson, Yenan
      Lau, Yu-Lung
      Itan, Yuval
      Cobat, Aurélie
      Casanova, Jean-Laurent
      Date
      2022-03-24
      Source Title
      Nature
      Print ISSN
      0028-0836
      Electronic ISSN
      1476-4687
      Publisher
      Springer Nature
      Volume
      603
      Issue
      7902
      Pages
      587 - 598
      Language
      English
      Type
      Article
      Item Usage Stats
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      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 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. © 2022, Springer Nature Limited.
      Keywords
      Age Distribution
      Autoantibodies
      COVID-19
      Critical Illness
      Dendritic Cells
      Genome-Wide Association Study
      Humans
      Interferon Type I
      Sex Distribution
      Toll-Like Receptor 3
      Toll-Like Receptor 7
      Permalink
      http://hdl.handle.net/11693/111756
      Published Version (Please cite this version)
      https://dx.doi.org/10.1038/s41586-022-04447-0
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