10x 16plex flex scRNAseq with either uninfected or SARS-CoV-2 infected mouse lungs from WT or Ccr2-/- mice

Respiratory viral infections caused by SARS-CoV-2 and Influenza virus pose significant public health concerns, with severe outcomes for at-risk and even healthy patients. While disease severity is often associated with dysregulated monocyte-macrophage activities in patients, emerging evidence highlights the active role of infected epithelial cells in early viral defense with subsequent implications on disease severity. We assessed the contribution of monocytes to host defense against respiratory viral infections and discovered that Ccr2-/- mice exhibited a markedly worsened outcome, increased viral load and more severe lung damage following SARS-CoV-2 infection compared to WT animals. WT bone marrow transplanted in Ccr2-/- mice could not mitigate disease severity upon SARS-CoV-2 infection. To assess cell type specific responses to SARS-CoV-2 in the presence and absence of monocyte recruitment, we sorted viable CD45+ and CD45- cells from uninfected and SC2-infected WT and Ccr2-/- lungs and performed single-cell RNA sequencing (scRNAseq) at day 1 post infection at a time point when monocyte recruitment is still limited even in WT mice. We found that Ccr2-/- mice mount an exaggerated inflammatory response as early as day 1 post SC2 infection in all cell types, with limited changes at baseline.