Fig. 7: Molecular basis underlying pulmonary endotheliopathy in the lungs of patients with COVID-19.

a, UMAP plots showing subtypes of CLDN5⁺ endothelial cells in the lungs of the Control and COVID-19 groups; n = 4,500 cells in each. b, Proportions of endothelial cell subtypes in the lungs of the Control and COVID-19 groups. The P value, determined using a Wilcoxon signed-rank test, is indicated. c, Ridge map showing increased death scores in different endothelial cell subtypes in the lungs of patients with COVID-19 compared with those of the Control group. d, Expression levels of endothelial damage-related genes in different endothelial cell subtypes. e, Heatmaps showing the upregulated COVID-19 DEGs related to inflammation in the different endothelial cell subtypes. f, Reconstruction of the transcriptional regulon network linking core regulatory transcription factors to potential target genes of the indicated pathways. g, Cell-cell interactions between immune cells and various endothelial cell subtypes. h, UMAP plots showing the expression levels of genes related to pro- (top) and anti-coagulation (bottom) in different endothelial cell subtypes in the lungs of the Control and COVID-19 groups. i, Gene-set core analysis of pro- (left) and anti-coagulation (right) pathways in individual cells of distinct endothelial cell subtypes. j, Diagram of the coagulation (left) and fibrinolysis (right) pathways (top). The values below the gene names indicate the log₂FC value at the RNA (left) and protein (right) levels. Heatmap showing the expression levels of the indicated genes in the lungs of patients with COVID-19 (bottom). k, Schematic showing the vascular pathological changes in the lungs of patients with COVID-19. AM.M1, M1 alveolar macrophage; AM.M2, M2 alveolar macrophage; IM.M1, M1 interstitial macrophage; IM.M2, M2 interstitial macrophage; Pro.mono, proliferative monocyte; Mono.macro, mononuclear macrophage; and the remaining cell-type abbreviations as per Fig. 2a.