A Spatiotemporal Dynamic Immune Landscape of the COVID-19 Hamster Lung [M][sc]

Although SARS-CoV-2-mediated inflammation has attracted global health concerns since 2019, its pulmonary immunopathology is not fully understood. Here we generated a comprehensive cellular and molecular landscape of healthy and COVID-19 hamster lungs at different timepoints after infection, using single-cell RNA sequencing and spatial transcriptomic sequencing to map the entire progression of COVID-19. We found SARS-CoV-2 could infect naive T cells and induced cell death to decrease T cell number at the early stage of COVID-19. Besides, we observed the activation and depletion of tissue resident myeloid cells after infection, the accumulation of Isg12+Cst7+ neutrophils and Il10+Spp1+M2-like macrophages to clean up virus and resolve inflammation. Finally, we identified Trem2+AM and Fbp1+AM subsets during the resolution stage of COVID-19. Our study provided spatiotemporally-resolved insights into the lung cells transcriptome, identified distinct tissue regions of viral infection, lung injury, repair and remodeling.