TY - JOUR
T1 - Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
AU - NIAID-USUHS/TAGC COVID Immunity Group
AU - COVID Clinicians
AU - Imagine COVID Group
AU - COVID-STORM Clinicians
AU - COVID-STORM Clinicians
AU - French COVID Cohort Study Group
AU - CoV-Contact Cohort
AU - Amsterdam UMC Covid-19 Biobank
AU - COVID Human Genetic Effort
AU - Zhang, Qian
AU - Liu, Zhiyong
AU - Moncada-Velez, Marcela
AU - Chen, Jie
AU - Ogishi, Masato
AU - Bigio, Benedetta
AU - Yang, Rui
AU - Arias, Andrés Augusto
AU - Zhou, Qinhua
AU - Han, Ji Eun
AU - Ugurbil, Aileen Camille
AU - Zhang, Peng
AU - Rapaport, Franck
AU - Li, Juan
AU - Spaan, András N.
AU - Boisson, Bertrand
AU - Boisson-Dupuis, Stéphanie
AU - Bustamante, Jacinta
AU - Puel, Anne
AU - Ciancanelli, Michael J.
AU - Zhang, Shen Ying
AU - Béziat, Vivien
AU - Jouanguy, Emmanuelle
AU - Abel, Laurent
AU - Cobat, Aurélie
AU - Casanova, Jean Laurent
AU - Bastard, Paul
AU - Korol, Cecilia
AU - Rosain, Jérémie
AU - Philippot, Quentin
AU - Chbihi, Marwa
AU - Lorenzo, Lazaro
AU - Bizien, Lucy
AU - Neehus, Anna Lena
AU - Kerner, Gaspard
AU - Seeleuthner, Yoann
AU - Manry, Jeremy
AU - Le Voyer, Tom
AU - Boisson, Bertrand
AU - Boisson-Dupuis, Stéphanie
AU - Bustamante, Jacinta
AU - Puel, Anne
AU - Zhang, Shen Ying
AU - Béziat, Vivien
AU - Jouanguy, Emmanuelle
AU - Abel, Laurent
AU - Cobat, Aurélie
AU - Bastard, Paul
AU - Feldman, Hagit Baris
AU - Feldman, Hagit Baris
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/10/23
Y1 - 2020/10/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85094120212&partnerID=8YFLogxK
U2 - 10.1126/science.abd4570
DO - 10.1126/science.abd4570
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C2 - 32972995
AN - SCOPUS:85094120212
SN - 0036-8075
VL - 370
JO - Science
JF - Science
IS - 6515
M1 - eabd4570
ER -
