Delayed engagement of host defenses enables SARS-CoV-2 viremia and productive infection of distal organs

SARS-CoV-2, the aetiologic agent of COVID-19, directly antagonizes these defenses, resulting in a delay of immune engagement in the lungs that materializes only as cells succumb to infection and are phagocytosed. Leveraging the golden hamster model of COVID-19, we sought to understand the dynamics between SARS-CoV2 infection in the airways and the systemic host response that ensues.

We find that early SARS-CoV-2 replication is largely confined to the respiratory tract and olfaction system, and, to a lesser extent, the heart and GI tract­­­, but generates a host antiviral response that can be observed in every organ as a result of circulating type I and III interferons (IFN-I/-III). Moreover, we show that diminishing the response in the airways by immunosuppression or administration of SARS-CoV-2 intravenously, results in a loss of immune priming, viremia, and an increase in viral tropism, including productive infection of the liver, kidney, spleen, and brain.