Figure 4.
Identification of biomarkers of COVID-19 severity associated with CH mutations. (A) Overview of COVID-19 cohorts without CH (CH−), TET2mt CH, and DNMT3Amt CH, analyzed using scRNA-seq. Mutations and VAFs are shown above, and patient ages are shown below, the figurines. Sample identifier is shown inside the figurines. (B) UMAP projections showing the distribution of 78 083 cells from scRNA-seq analysis from 24 patient samples, colored by cell types identified using SingleR. The bar below shows the proportion of cells in each cell type. (C) Proportion of cells in each cell type stratified by 5 conditions as shown in y-axis, in the scRNA-seq analysis. The healthy cohort (from Stephenson et al40) is further stratified by age: <50 and >50 years, respectively. (D) Volcano plot showing significantly differentially expressed genes (adjusted P < .05, Wilcoxon rank sum test) in comparisons between TET2mt CH and DNMT3Amt CH in the context of COVID-19. Cells from each cell type were tested independently. Bars below the volcano plots show the proportion of genes per cell type that are downregulated and upregulated in the DNMT3Amt CH in each comparison. (E) Violin plots showing expression of IL-32 in cell types in which, patients with DNMT3Amt CH had significantly higher expression of IL-32 in comparison to those with TET2mt CH. Black dots show mean expression. ∗∗∗∗P ≤ .0001 (Wilcoxon rank sum test). (F) Survival analysis separating patients showing IL-32 high and low (upper tertile and lower quartiles respectively) in protein level profiles using the Olink assay. Inset plot shows the IL-32 Olink measurements reported as normalized protein expression (NPX) values, with a 1-unit increase equating to a doubling of the protein concentration. This analysis shows that patients with higher levels of IL-32 in their serum had worse OS. cDC, classical dendritic cells; gdT, γδ T cells; Int, intermediate; MAIT, mucosal-associated invariant T cells; Max, maximum; Min, minimum; Mono, monocytes; pDC, plasmacytoid dendritic cells; SD, standard deviation; Treg, regulatory T cells.

Identification of biomarkers of COVID-19 severity associated with CH mutations. (A) Overview of COVID-19 cohorts without CH (CH−), TET2mt CH, and DNMT3Amt CH, analyzed using scRNA-seq. Mutations and VAFs are shown above, and patient ages are shown below, the figurines. Sample identifier is shown inside the figurines. (B) UMAP projections showing the distribution of 78 083 cells from scRNA-seq analysis from 24 patient samples, colored by cell types identified using SingleR. The bar below shows the proportion of cells in each cell type. (C) Proportion of cells in each cell type stratified by 5 conditions as shown in y-axis, in the scRNA-seq analysis. The healthy cohort (from Stephenson et al40) is further stratified by age: <50 and >50 years, respectively. (D) Volcano plot showing significantly differentially expressed genes (adjusted P < .05, Wilcoxon rank sum test) in comparisons between TET2mt CH and DNMT3Amt CH in the context of COVID-19. Cells from each cell type were tested independently. Bars below the volcano plots show the proportion of genes per cell type that are downregulated and upregulated in the DNMT3Amt CH in each comparison. (E) Violin plots showing expression of IL-32 in cell types in which, patients with DNMT3Amt CH had significantly higher expression of IL-32 in comparison to those with TET2mt CH. Black dots show mean expression. ∗∗∗∗P ≤ .0001 (Wilcoxon rank sum test). (F) Survival analysis separating patients showing IL-32 high and low (upper tertile and lower quartiles respectively) in protein level profiles using the Olink assay. Inset plot shows the IL-32 Olink measurements reported as normalized protein expression (NPX) values, with a 1-unit increase equating to a doubling of the protein concentration. This analysis shows that patients with higher levels of IL-32 in their serum had worse OS. cDC, classical dendritic cells; gdT, γδ T cells; Int, intermediate; MAIT, mucosal-associated invariant T cells; Max, maximum; Min, minimum; Mono, monocytes; pDC, plasmacytoid dendritic cells; SD, standard deviation; Treg, regulatory T cells.

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