Data of the SARS-CoV-2 adaptation in type I and III IFN deficient mice

The disease severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe COVID-19 and show that the age-dependent disease severity is caused by the disruption of a timely and well-coordinated innate and adaptive immune response due to impaired interferon (IFN) responses. Aggravated disease in aged mice was characterized by a diminished IFN-? response and excessive virus replication. Accordingly, adult IFN-? receptor-deficient mice phenocopied the age-related disease severity and supplementation of IFN-? reversed the increased disease susceptibility of aged mice. Mimicking impaired type I IFN immunity in adult and aged mice, a second major risk factor for severe COVID-19, we found that therapeutic treatment with IFN-? in adult and a combinatorial treatment with IFN-? and IFN-? in aged Ifnar1-/- mice was highly efficient in protecting against severe disease. Our findings provide an explanation for the age-dependent disease severity and clarify the nonredundant antiviral functions of type I, II and III IFNs during SARS-CoV-2 infection in an age-dependent manner. Based on our data, we suggest that highly vulnerable individuals combining both risk factors, advanced age and an impaired type I IFN immunity, may greatly benefit from immunotherapy combining IFN-? and IFN-?.