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  4. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
 
research article

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Zhang, Qian
•
Bastard, Paul
•
Liu, Zhiyong
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October 23, 2020
Science

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.

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Type
research article
DOI
10.1126/science.abd4570
Web of Science ID

WOS:000581077200034

Author(s)
Zhang, Qian
Bastard, Paul
Liu, Zhiyong
Le Pen, Jeremie
Moncada-Velez, Marcela
Chen, Jie
Ogishi, Masato
Sabli, Ira K. D.
Hodeib, Stephanie
Korol, Cecilia
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Date Issued

2020-10-23

Publisher

American Association for the Advancement of Science

Published in
Science
Volume

370

Issue

6515

Start page

422

Subjects

Multidisciplinary Sciences

•

Science & Technology - Other Topics

•

herpes-simplex encephalitis

•

nf-kappa-b

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deficiency

•

susceptibility

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPFELLAY  
Available on Infoscience
November 5, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/172998
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