(a) The UMAP presentation of the heterogenous clusters of BALF macrophages. Cluster 12 (CD68+CD3D+), 18 (CD68+IGHG4+) and 19 (CD68+IGHG4+) were excluded in the following analysis (n = 13). (b) UMAP plots showing the expression of several markers on BALF macrophages. The markers on top and bottom panels indicate the existence of heterogeneous macrophages (n = 13). (c) The BALF macrophage clusters were classified to 4 groups according to FCN1, SPP1 and FABP4 expression levels, indicated by grey dashed lines (n = 13). (d) The UMAP projection of FCN1, SPP1, and FABP4 expressing cells among controls (n = 4) and patients (n = 3 for moderate patients, n = 6 for severe/critical patients). (e) The heatmaps of hierarchically clustered top 50 differentially-expressed genes (DEGs) across 4 groups of macrophages. The gene names were listed to the right. (f) The GO analysis of up-regulated DEGs showing some highlighted pathways in the four groups of macrophages (n = 13, hypergeometric test, adjusted p-values obtained by Benjamini-Hochberg procedure). (g) The GSEA NES heatmap of the 50 MSigDB hallmark gene sets across 4 groups of macrophages. The gene list for each group was ordered based on signal-to-noise ratio of this group compared with all other cells. Default parameters in GSEA function of clusterProfiler were used (except nPerm = 100, 000, Kolmogorov-Smirnov test). (h) Average regulon activities of 4 groups of macrophages calculated with SECENIC. PySCENIC was used to infer co-expression modules, prune modules for targets with cis regulatory footprints and calculate cellular regulon enrichment matrix with default parameters.