Fig. 5: Monocyte-to-macrophage differentiation in COVID-19 BAL.

a Subclustering of myeloid cells into 9 phenotypes, as indicated by the color-coded legend. b Heatmap showing myeloid cell phenotypes with corresponding functional gene sets. c Relative contribution of each cell type (in %) to COVID-19 vs non-COVID-19 BAL. d Relative contribution of each cell type (in %) to mild vs critical COVID-19 BAL. e Pseudotime trajectories for myeloid cells based on Slingshot, showing the common branch of FCN1^hi monocytes differentiating into either RGS1^hi monocyte-derived macrophages (RGS1^hi-lineage) or FABP4^hi tissue-resident alveolar macrophages (alveolar lineage). f Profiling of marker genes along these trajectories to confirm their functional annotation: FCN1, S100A12, CCL2, CCL18 for the common branch, FABP4 and PPARG for the alveolar lineage, RGS1 and GPR183 for the RGS1-lineage. g Density plots reflecting the number of myeloid cells along the 2 lineages stratified for non-COVID-19 vs COVID-19. h Density plots reflecting the number of myeloid cells along the 2 lineages stratified for mild vs critical COVID-19. i Gene expression dynamics along the alveolar lineage. Genes cluster into 5 gene sets, each of them characterized by specific expression profiles, as depicted by a selection of genes characteristic for each cluster. j Normalized ATP level measured from BAL supernatans comparing COVID-19 vs non-COVID-19 (left) and mild vs critical COVID-19 patients (right). k–m Profiling of IFN type I and II signaling along the 3 CD8⁺ (k) and CD4⁺ (l) T-cell lineages, and along the monocyte-macrophage lineage (m), comparing mild vs critical COVID-19. All P values were assessed by a Mann–Whitney test. *P < 0.05, **P < 0.01, ***P < 0.001. P values comparing COVID-19 vs non-COVID-19, and mild vs critical COVID-19 for density plots were all < 10E-50.