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

Science, 24 September, 2020

Qian Zhang, Paul Bastard, Zhiyong Liu, Jérémie Le Pen, Marcela Moncada-Velez, Jie Chen, et al.

Highlights:

• 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.

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