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

Zhang, Q; Bastard, P; Liu, ZY; Le Pen, J; Moncada-Velez, M; Chen, J; Ogishi, M; Sabli, IKD; Hodeib, S; Korol, C; Rosain, J; Bilguvar, K; Ye, JQ; Bolze, A; Bigio, B; Yang, R; Arias, AA; Zhou, QH; Zhang, Y; Onodi, F; Korniotis, S; Karpf, L; Philippot, Q; Ch

SCIENCE
2020
VL / 370 - BP / 422 - EP / +
abstract
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.

AccesS level

Green Published, Other Gold

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PROYECTO FINANCIADO POR PLAN NACIONAL DE INVESTIGACIÓN AGENCIA ESTATAL DE INVESTIGACIÓN, MINISTERIO DE CIENCIA E INNOVACIÓN. PID2019-109127RB-I00