Fig. 3: Activation of downstream pathways associated with pro-inflammatory cytokines is correlated with defective IFN responses in severe COVID-19 APCs from the discovery set.

a, Violin plot representation of cytokine (IL1B, TGFB1 and IL-18) receptor (IL6R, TNFRSF1A) and chemokine (CXCL8) gene expression levels detected by scRNAseq and comparison between severity groups. Each dot represents a cell and horizontal lines display the mean expression value. b, Dot plot of enrichment scores of pathways downstream of IL-1B, IL-6 and TGFB1 inflammatory cytokines; score levels are colour-coded, and the percentage of cells expressing the pathway score is size-coded. c, Heatmap representation of expression levels of IFN genes (ligands and receptors) and ISG expression levels in healthy, moderate and severe APCs. Expression levels are colour-coded. d, Dot plots of regulators of IFN signalling and antiviral ISG genes in HCs and patients with moderate and severe COVID-19. Expression levels are colour-coded, and the percentage of cells expressing the respective gene is size-coded. e, Violin plot representation of antiviral ISGs among the severity groups; the small horizontal line indicates the mean expression value for each plotted gene expression. In a and e, the violin plots were designed using the total APC subsets from the discovery set (n = 42,784 cells), composed of n = 2 HC, n = 4 moderate and n = 6 severe samples. Comparative analysis was performed using the two-sided Wilcoxon rank-sum test; P values were adjusted to multiple testings using ‘Bonferroni’ correction. Asterisks above severe indicate P values for severe versus control; asterisks above moderate indicate significance of moderate versus control. *P < 0.05, **P < 0.01, ***P < 0.001; NS, not significant.