Fig. 3: Single-cell analysis of consensus endotypes.

a, Integration of 4 whole-blood scRNA-seq datasets from patients with COVID-19 and sepsis, inclusive of the neutrophil compartment and identifying 14 unique cell types using the Seurat and Scanpy pathways. The UMAP of cell types is shown. b, Evaluation of scaled gene expression signatures across these cell types, showing that the scores included in each consensus molecular endotype were expressed in similar cell types. The red cluster (MARS2, SoM module 1 or 2, Sweeney inflammopathic, Yao innate and SRS signatures) was predominantly expressed with immature neutrophils. The blue cluster (MARS3, Yao adaptive, Sweeney adaptive and SoM module 4) was predominantly expressed in T or NK cells. The purple cluster (MARS1, Sweeney coagulopathic and Yao coagulopathic) was a mix of intermediate expression of neutrophils and T or NK cells. The green cluster (MARS4, Wong score and SoM module 3) was predominantly expressed in mature neutrophils and monocytes. c, Development of a cell-type-specific score by evaluating scaled expression of each gene across all endotype signatures and selecting 104 genes that were selectively expressed (defined by >1 s.d. greater than other cell types evaluated) in myeloid or T or NK cell types. We then divided these genes into detrimental or protective genes based on whether the signature from which they were derived was associated with worse or better outcomes in prior studies. cDC, classical dendritic cell; HSPC, hematopoietic stem and progenitor cell; PB, peripheral blood; pDC, plasmacytoid dendritic cell.