Plasmacytoid dendritic cells from IRF7-deficient patients produced no type I IFN on infection with SARS-CoV-2, and TLR3−/−, TLR3+/−, IRF7−/−, and IFNAR1−/− fibroblasts were susceptible to SARS-CoV-2 infection in vitro. Here, TLR3 is linked to infection.