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23 octobre 2020
- doi: 10.1126/science.abd4570
- issn: 0036-8075
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info:eu-repo/semantics/altIdentifier/doi/10.1126/science.abd4570
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info:eu-repo/semantics/altIdentifier/pmid/32972995
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info:eu-repo/semantics/altIdentifier/eissn/1095-9203
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_38514EC06F0A1
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Q. Zhang et al., « Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. », Serveur académique Lausannois, ID : 10.1126/science.abd4570
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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.