Fig. 4: Innate immune cells dominate early peripheral immune responses and predict survival in critical COVID-19.

a UMAP embedding plot of CD14 monocytes, CD16 monocytes, and cDC2 cells for the following sample conditions: Control, Alive day 0, and Deceased day 0. b Hierarchical clustering heatmap of average normalized gene expression for statistically significant differentially expressed genes (adjusted p-value < 0.05 and log2FC > 0.50) between Control, Alive day 0 and Deceased day 0 CD14 monocytes, CD16 monocytes, and cDC2 cells. UMAP embedding plots and quantification for Control, Alive day 0, and Deceased day 0 samples for c inflammatory activation gene set z-scores, d antigen-presentation gene set z-scores, e ISG set z-scores, and f protein synthesis gene set z-scores from genes in b. All comparisons were statistically significant (p < 0.0001) except the ones marked n.s. g Random forest classifier model survival prediction accuracy using 3000 highly variable gene normalized counts in all cell types with at least 100 cells. Red boxed cell types are those with a prediction accuracy of >80%. h Ranked feature importance score from random forest classifier model with key genes annotated in CD14 monocytes (top), CD16 monocytes (middle), and cDC2 cells (bottom). i Global UMAP embedding plot of the top 100 predictive features in CD14 monocytes, CD16 monocytes, and cDC2 cells for Control (top), Alive day 0 (middle), and Deceased day 0 (bottom). j Venn diagram of overlapping genes from the top predictive features for the CD14 monocytes random forest classifier, statistically significant differentially expressed genes between Alive day 0 and Deceased day 0 CD14 monocytes, and statistically significant differentially expressed genes between Control and day 0 CD14 monocytes. k UMAP embedding plot from a of Control (left, top), Alive day 0 (left, middle), and Deceased day 0 (left, bottom) for four overlapping genes (CEBPD, MAFB, IFITM3, and LGALS1) identified from j with z-score quantification (right). On all heatmaps blue (low) to red (high) expression.12,044 Control, 8530 Alive day 0, and 5385 Deceased day 0 CD14 Monocytes were examined across 18 patients. 1694 Control, 1559 Alive day 0, and 1216 Deceased day 0 CD16 Monocytes were examined across 18 patients. 553 Control, 108 Alive day 0, and 104 Deceased day 0 cDC2 cells were examined across 18 patients. Ordinary one-way ANOVA statistical tests were used for each comparison. **** denotes p < 0.0001.