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Fig. 2 | Journal of Hematology & Oncology

Fig. 2

From: Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology

Fig. 2

Subcluster analysis of peripheral blood CD8+ T cells in COVID-19 patients: activation following SARS-CoV-2 infection is dampened by CD24Fc treatment. 1,466,822 CD8+ cells from HD (n = 17) and COVID-19 (n = 22) patients were clustered using an unbiased multivariate t-mixture model, which identified eight statistically distinct CD8+ sub-clusters that reflect different activation states. The relative similarity of each cell and cell cluster on the two-dimensional UMAP space were visualized with a 10% downsampling (A). Using median expression of flow cytometry markers, a cluster-by-marker heatmap was generated to characterize the subsets (B) and visualize individual marker expression patterns on the UMAP space (C). To understand the effect of SARS-CoV-2 infection on cell population dynamics, a comparison was made with UMAP plots (D) and cluster frequencies (E) of HD vs. baseline COVID-19 patient samples (p < 0.001 for clusters 1, 4, 5, 7, 8). The samples from COVID-19 patients 2, 4, and 8 days after CD24Fc vs. placebo are displayed using contour plots to represent density of cells throughout regions of the UMAP space (F, white arrows indicate visual changes between CD24Fc vs. placebo). Cluster population dynamics as fold change over baseline in each treatment group are shown (G; sample distribution described in Fig. 1F; p < 0.001 for cluster 1–8). To better characterize the activation status of CD8 T cells, a subset of markers (T-bet, Ki-67, CD69, TOX, GZMB) was linearly transformed to create a univariate cell-level activation score (H), where highly activated cell clusters (such as cluster 8) had highest activation scores (I). A GLMM was fit to the longitudinal cell-level activation scores to assess the effect of CD24Fc treatment on activation scores over time (J). The p-values in E and J were calculated using Wilcoxon rank-sum test and Kenward-Roger method, respectively. ***p < 0.001

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