Several main performers of innate immunity, such as signal transducer and activator of transcription 1 (STAT1), myeloid differentiation primary response gene 88 (MyD88), Toll-like receptor (TLR)4, TLR7, and TLR3/TIR-domain-containing adapter-inducing interferon-beta (TRIF) diminish infection severity during HCoV infection in vivo. This evidence concerns the gene STAT1 and infection.