Science, 24 September, 2020
, et al.
- Found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and 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.
- Experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies.
- Human fibroblasts with mutations affecting this pathway 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.