Leveraging the antiviral type-I interferon system as a first line defense against SARS-CoV-2 pathogenicity

Hoagland, Daisy A.; Møller, Rasmus; Uhl, Skyler A.; Oishi, Kohei; Frere, Justin; Golynker, Ilona; Horiuchi, Shu; Panis, Maryline; Blanco-Melo, Daniel; Sachs, David; Arkun, Knarik; Lim, Jean K.; tenOever, Benjamin R.

The emergence and spread of SARS-CoV-2 has resulted in significant global morbidity, mortality, and societal disruption. A better understanding of virus-host interactions may potentiate therapeutic insights toward limiting this infection. Here, we investigated the dynamics of the systemic response to SARS-CoV-2 in hamsters by histological analysis and transcriptional profiling. Infection resulted in consistently high levels of virus in both the upper and lower respiratory tracts and sporadic occurrences in other distal tissues. A longitudinal cohort revealed a wave of inflammation including a Type-I interferon (IFN-I) response that was evident in all tissues regardless of viral presence, but was insufficient to prevent disease progression. Bolstering the antiviral response with intranasal administration of recombinant IFN-I reduced viral disease, prevented transmission, and lowered inflammation in vivo. This study defines the systemic host response to SARS-CoV-2 infection and supports use of intranasal IFN-I as an effective means of early treatment.