The authors therefore assessed the presence of rare variants in 13 genes known to affect the Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity pathways in 659 patients with life-threatening COVID-19, defined as critical disease with respiratory insufficiency requiring mechanical ventilation or high-flow oxygen, septic shock or other organ damage requiring critical care in ICU, compared to 534 individuals with asymptomatic or mild SARS-CoV-2 infection [51]. This evidence concerns the gene IRF7 and Respiratory insufficiency.