In this preprint, Boudewijns et al. examined the interferon (IFN) response in Syrian hamsters, which develop significant lung pathology after SARS-CoV-2 infection, and in C57BL/6 mice, which do not. However, SARS-CoV-2-infected Ifnar1–/– mice had an increased infiltration of inflammatory cells in the lung, suggesting that an active, functional and immediate type I IFN response restricts pathogenesis in mice. The analysis of hamsters with a deletion of Stat2 (which causes a loss of type I and type III IFN signalling) or of Il28r (resulting in loss of type III IFN signalling alone) suggested that type III IFNs help to restrict viral dissemination, whereas type I IFNs exacerbate bronchopneumonia in hamsters. These opposing roles warrant further study, and the histological findings suggest that the Syrian hamster is a better model for COVID-19 than the mouse.