TY - JOUR
T1 - Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
AU - Zhang, Qian
AU - Bastard, Paul
AU - Liu, Zhiyong
AU - Le Pen, Jérémie
AU - Moncada-Velez, Marcela
AU - Chen, Jie
AU - Ogishi, Masato
AU - Sabli, Ira K.D.
AU - Hodeib, Stephanie
AU - Korol, Cecilia
AU - Rosain, Jérémie
AU - Bilguvar, Kaya
AU - Ye, Junqiang
AU - Bolze, Alexandre
AU - Bigio, Benedetta
AU - Yang, Rui
AU - Arias, Andrés Augusto
AU - Zhou, Qinhua
AU - Zhang, Yu
AU - Onodi, Fanny
AU - Korniotis, Sarantis
AU - Karpf, Léa
AU - Philippot, Quentin
AU - Chbihi, Marwa
AU - Bonnet-Madin, Lucie
AU - Dorgham, Karim
AU - Smith, Nikaïa
AU - Schneider, William M.
AU - Razooky, Brandon S.
AU - Hoffmann, Hans Heinrich
AU - Michailidis, Eleftherios
AU - Moens, Leen
AU - Han, Ji Eun
AU - Lorenzo, Lazaro
AU - Bizien, Lucy
AU - Meade, Philip
AU - Neehus, Anna Lena
AU - Ugurbil, Aileen Camille
AU - Corneau, Aurélien
AU - Kerner, Gaspard
AU - Zhang, Peng
AU - Rapaport, Franck
AU - Seeleuthner, Yoann
AU - Manry, Jeremy
AU - Masson, Cecile
AU - Schmitt, Yohann
AU - Schlüter, Agatha
AU - Le Voyer, Tom
AU - Khan, Taushif
AU - Al-Mulla, Fahd
N1 - Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
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
M3 - Article
C2 - 32972995
AN - SCOPUS:85094120212
VL - 370
JO - Science
JF - Science
SN - 0036-8075
IS - 6515
ER -