Single cell sequencing reveals infection dynamics in lungs of African green monkeys infected with SARS-CoV-2

Studying the dynamics of SARS-CoV-2 infection in vivo is important to determine virus and host response factors that may play a role in pathogenesis. Controlled studies that include collection of time-resolved, multiple sampling days is not possible in humans and thus animal models of disease are essential to fill in the gaps in our understanding of disease progression. African green monkeys recapitulate mild COVID-19 cases, thereby serving as an important model for studying disease pathogenesis. In this study, we utilize the African green monkey model of SARS-CoV-2 infection and compare SARS-CoV-2-infected animals to animals inoculated with a gamma-irradiated form of the virus to study the dynamics of virus replication throughout the respiratory tract and other target tissues. We included single-cell sequencing of the lungs and mediastinal lymph nodes, allowing a high-resolution, simultaneous analysis of virus replication and the host response in these tissues over time. We found that viral genomic RNA (gRNA) is highly stable especially in the upper respiratory tract even without the presence of replicating virus. Additionally, we found that virus mainly replicates in the lower respiratory tract, mainly in the pneumocyte population. Additional analysis of the host response to infection showed that macrophages are playing vital and dynamic roles in initiating a pro-inflammatory state in the lungs, as well as interacting with infected pneumocytes. Together, our dataset provides a unique view of the changes in the host and virus replication dynamics over the course of a mild COVID-19 infection through to early stages of recovery and will be a valuable resource to identify new therapeutic targets.