Extended Data Fig. 7: Donor-specific enrichment of SARS-CoV-2 RNA⁺ cells and host responses to viral RNA.

a–d, SARS-CoV-2 RNA⁺ cells are enriched in specific lineages and subtypes. a, c, UMAP embeddings of either myeloid cells (a), or endothelial cells (c) from seven donors containing any SARS-CoV-2 RNA⁺ cell, and coloured by viral enrichment score (colour bar; red, stronger enrichment) and by SARS-CoV-2 RNA⁺ cells (black points). b, d, Number of SARS-CoV-2 RNA⁺ cells (y axis) per cell type/subset (x axis) in myeloid (b) or endothelial (d) subsets. Bar colour, FDR (dark blue, higher significance, Supplementary Methods; *FDR < 0.05). e–h, Variation across donors. e–g, UMAP embeddings of sc/snRNA-Seq profiles from each of seven donors containing any SARS-CoV-2 RNA⁺ cell (columns), coloured by major cell categories (e), expression of SARS-CoV-2 entry factors (f) or SARS-CoV-2 RNA enrichment per cluster (g, red/blue colour bar; red, high enrichment; black points, SARS-CoV-2 RNA⁺ cells). h, Number of SARS-CoV-2 RNA⁺ cells (y axis) across major cell types (x axis) from each of seven donors containing any SARS-CoV-2 RNA⁺ cell (columns). Bar colour, FDR (dark blue, higher significance). *FDR < 0.05. i, j, Normalized enrichment score (bars, right y axis) and significance (points, FDR, left y axis) (by GSEA^39,40, Supplementary Methods) of different functional gene sets (x axis) in genes upregulated in SARS-CoV-2 RNA⁺ epithelial (i) or myeloid (j) cells. k, Expression of SARS-CoV-2 genomic features (log-normalized UMI counts; rows) across SARS-CoV-2 RNA⁺ (k = 158 cells) and SARS-CoV-2 RNA⁻ (k = 790) myeloid cells (columns). l, m, Distribution of normalized expression levels (y axis) for select significantly differentially expressed genes between SARS-CoV-2 RNA⁻ and SARS-CoV-2 RNA⁺ cells from all myeloid cells or CD14^highCD16^high inflammatory monocytes. DGE, differential gene expression.

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