Although the host response to SARS-CoV highlighted a role for IFNs, most studies assessed the effect of IFN restriction in cell lines that might not fully recapitulate the repertoire of ISGs present in primary human target cells (Bailey et al., 2014, de Lang et al., 2006, Sainz et al., 2004, Zheng et al., 2004). One study of SARS-CoV suggested the timing of the type I IFN response was critical in vivo (Channappanavar et al., 2016). Clinical therapy using approved IFNs has been attempted for SARS-CoV, MERS-CoV, and SARS-CoV-2 in the absence of a controlled trial to mixed effect, resulting in anecdotal evidence suggesting either rapid improvement or worsening of symptoms (Dong et al., 2020b, Lei et al., 2020, Li and De Clercq, 2020). Elucidating tissue- and cell-type-specific ISGs and their activity is essential for understanding the role of IFNs in host defense during human SARS-CoV-2 infection.