The close association we observe between peak disease severity and weak anti-viral gene expression among nasal epithelial cells is intriguing given recent observations of inborn defects in TLR3, IRF7, IRF9, and IFNAR1, or antibody-mediated neutralization of type I IFN responses within individuals who develop severe COVID-19 (Bastard et al., 2020, 2021; Combes et al., 2021; Wang et al., 2021a; Zhang et al., 2020). This evidence concerns the gene IRF9 and COVID-19.