TY - JOUR
T1 - Human genetic and immunological determinants of critical COVID-19 pneumonia
AU - COVID Human Genetic Effort
AU - Zhang, Qian
AU - Bastard, Paul
AU - Karbuz, Adem
AU - Gervais, Adrian
AU - Tayoun, Ahmad Abou
AU - Aiuti, Alessandro
AU - Belot, Alexandre
AU - Bolze, Alexandre
AU - Gaudet, Alexandre
AU - Bondarenko, Anastasiia
AU - Liu, Zhiyong
AU - Spaan, András N.
AU - Guennoun, Andrea
AU - Arias, Andres Augusto
AU - Planas, Anna M.
AU - Sediva, Anna
AU - Shcherbina, Anna
AU - Neehus, Anna Lena
AU - Puel, Anne
AU - Froidure, Antoine
AU - Novelli, Antonio
AU - Parlakay, Aslınur Özkaya
AU - Pujol, Aurora
AU - Yahşi, Aysun
AU - Gülhan, Belgin
AU - Bigio, Benedetta
AU - Boisson, Bertrand
AU - Drolet, Beth A.
AU - Franco, Carlos Andres Arango
AU - Flores, Carlos
AU - Rodríguez-Gallego, Carlos
AU - Prando, Carolina
AU - Biggs, Catherine M.
AU - Luyt, Charles Edouard
AU - Dalgard, Clifton L.
AU - O’Farrelly, Cliona
AU - Matuozzo, Daniela
AU - Dalmau, David
AU - Perlin, David S.
AU - Mansouri, Davood
AU - van de Beek, Diederik
AU - Vinh, Donald C.
AU - Dominguez-Garrido, Elena
AU - Hsieh, Elena W.Y.
AU - Erdeniz, Emine Hafize
AU - Jouanguy, Emmanuelle
AU - Şevketoglu, Esra
AU - Talouarn, Estelle
AU - Quiros-Roldan, Eugenia
AU - Feldman, Hagit Baris
N1 - Publisher Copyright:
© 2022, Springer Nature Limited.
PY - 2022/3/24
Y1 - 2022/3/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124267100&partnerID=8YFLogxK
U2 - 10.1038/s41586-022-04447-0
DO - 10.1038/s41586-022-04447-0
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C2 - 35090163
AN - SCOPUS:85124267100
SN - 0028-0836
VL - 603
SP - 587
EP - 598
JO - Nature
JF - Nature
IS - 7902
ER -
