A Novel Single Cell RNA-seq Analysis of Circulating Immune Cells in Late Sepsis

With the successful implementation of guidelines from the Surviving Sepsis Campaign, in-hospital mortality to sepsis continues to decrease. However, this is has not lead to completely improved outcomes after sepsis. Up to 1/3 of sepsis survivors continue to have dismal long-term outcomes and 1-year mortality. Although the pathobiology of the dismal outcomes after sepsis remains undefined, it is thought that late after sepsis individuals enter a state of pathologic myeloid activation, inducing suboptimal lymphopoiesis and erythropoiesis, with many of the downstream immune cells being dysfunctional. The goal of this study was to use single-cell RNA sequencing to perform a detailed transcriptomic analysis of non-myeloid cells to better understand the pathology of late sepsis. Our findings highlight the unique transcriptomic pattern that circulating non-myeloid cells display 14 days after sepsis. Non-myeloid leukocytes in particular reveal an endotype of inflammation, immunosuppression and dysfunction. Immunomodulatory therapies at this late time point in sepsis may be feasible through precision medicine. Overall design: A mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from four late septic patients (post-sepsis day 14-21, RAP n=1 and CCI n=3) and five healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).