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cc by (c) Zhang et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/173758

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

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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.

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ZHANG, Qian, DORGHAM, Karim, SCHLÜTER, Agatha, QUIROS ROLDAN, Eugenia, NOVELLI, Giuseppe, PLANAS SERRA, Laura, RODRÍGUEZ PALMERO, Agustí, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. _Science_. 2020. Vol. 370, núm. 6515, pàgs. 422. [consulta: 21 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/173758]

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