Recent advances in single cell technology now allow researchers to simultaneously profile the transcriptional program and chromatin accessibility from individual cells, providing access to both the characterization of cell types and states, and the exploration of gene regulatory programs at the same time and in the same cells.
Here, we present an analysis of single cell transcriptomes and chromatin accessibility profiles in PBMCs from a group of SARS-COV-2 infected subjects with a range of disease severities. We were able to identify several immune cell types at a coarse level based on transcriptomic profiles. By additional subclustering, we found 4 clusters of CD8T cells which show differential distribution across COVID-19 severities. Analysis of DEGs revealed higher expression of genes associated with CD8 T cell terminal differentiation and effector functions in the cluster enriched in mild patients. Chromatin accessibility analysis of the selected DEGs in CD8T cells confirms higher accessibility in patients with mild disease vs severe patients. Interestingly, the transcripion factor ZEB2 was identified as one of the top markers of the mild-severity cluster. Further motif analysis will clarify the importance of this TF in CD8T cell differentiation and outcome in SARS-COV-2 infected subjects.