Loss-of-function variants of genes such as IRF3, IRF7, IFN-α receptor, and Toll-like receptor 3 (TLR3) were detected in 3.5% of individuals with life-threatening COVID-19 and no history of other severe infections, whereas no patient with mild or asymptomatic disease carried these variants; all of these variants resulted in disproportionately low IFN I production in response to SARS-CoV-2 (59). This evidence concerns the gene TLR3 and COVID-19.