Extended Data Fig. 9: Integrated network of plasma metabolites, plasma proteins, and genes involved in cell metabolic pathways.

(a) Plasma proteins and metabolites that were positively correlated with disease severity to generate a protein-metabolite network. (b) Levels of metabolic pathway-related transcripts were ranked at the patient pseudobulk level, and transcripts significantly positively correlated with WHO score were integrated with plasma metabolites that negatively correlated with WHO score to generate a gene-metabolite network. (c) Plasma proteins and metabolites that were negatively correlated with disease severity to generate a protein-metabolite network. (d) PCA of per-patient integrated plasma metabolites and metabolic pathways, performed on the cohort of 50 patient samples that had scRNA-seq data available. (e) PCA of per-patient integrated plasma metabolites and metabolic pathways, performed on the full cohort of patient samples. Dashed lines indicate well-separated clusters of patient samples by K-means clustering. Samples are colored by WHO score (left), hospitalization status (middle), and level of respiratory support (right). (f) Loading scores of cell type-specific metabolic pathway activities for PC1 and PC2 from the integrated PCA for cell types that did not exhibit strong metabolite signatures: CD8⁺ T cells and NK cells. (g) Pathway enrichment analysis of metabolites among the top five highest and lowest loading scores for each PC (Fig. 6d).