Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states [scRNA-Seq]

The ability of a virus to infect a cell type is partly determined by host factors required for the viral life cycle. However, not every cell of a given type is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the susceptible subsets of cells could reveal additional host factors, but viral infection dramatically alters the state of the cell, obscuring the state of these cells prior to infection. We used single-cell clone tracing to retrospectively identify cells that were highly susceptible to infection with SARS-CoV-2. Our approach revealed candidate factors playing roles in viral entry and regulation of the infectable cell state itself. Patient samples revealed heterogeneous expression of these factors in vivo, with heightened expression in particular inflammatory pathologies. Thus, variable expression of intrinsic cell states is a major determinant of whether individual cells can be infected by SARS-CoV-2. Overall design: Comparative gene expression profiling analysis of single-cell RNA-seq data for Calu-3 cells. Biological and technical replicates are included and indicated. Technical replicates refer to same biological replicate split amongst multiple lanes of the 10x chromium chip.