Fig. 6

CD24Fc treatment downregulates systemic cytokine response in patients with COVID-19. Relative differences in plasma concentrations of cytokines/chemokines between HD (n = 25) and COVID-19 patients (n = 22) is shown. Values were log-transformed and evaluated using independent sample t-test. Significantly up- and down-regulated markers are shown (A). Heatmap analysis (B) visualized relative levels of cytokines/chemokines (Placebo: D1 n = 12, D2 n = 12, D4 n = 11, D8 n = 5; CD24Fc: D1 n = 10, D2 n = 10, D4 n = 9, D8 n = 3). Using log-10 transformation of cytokine concentrations (dots) and GLMM-predicted fixed effects trends (lines), changes in IL-10 (C; p = 0.05) and IL-15 (D; p = 0.002) in CD24Fc (red) and placebo (black) groups were revealed. Values and trend lines were centered at D1 mean. p-value was calculated using the Kenward–Roger method. The cytokine score was analyzed longitudinally using weighed sum approach (E; p < 0.001). Using Pearson correlation matrices (F) and network maps (G; weight of edge represents correlation coefficient), 30 plasma markers in HD (n = 25), COVID-19 baseline (D1, n = 22), placebo (pooled D2–D8, n = 28), and CD24Fc-treated (pooled D2–D8, n = 24) groups were visualized. Using these correlation coefficients, a density plot (H; D1 vs placebo, p = 0.07; D1 vs CD24Fc, p < 0.001; placebo vs CD24Fc, p < 0.001) was constructed. Kolmogorov–Smirnov test was used to evaluate equality of densities between groups. Analysis of connectivity (I) and centrality analysis of cytokine network (J) display the cytokine expression relationships. Network connectivity plots display highly correlated connections for each cytokine (i.e., node degree) and was evaluated using paired t-test. Centrality analysis of cytokine network used eigenvector centrality score that considers global network connectivity and correlation coefficients between cytokines (HD vs D1, p < 0.001; D1 vs placebo, p = 0.08; D1 vs CD24Fc, p < 0.001). Bartlett’s test evaluated the significance of variance of centrality scores (HD vs D1, p = 0.013; D1 vs placebo, p = 0.17; D1 vs CD24Fc, p = 0.008). Each dot in I and J represents a cytokine. *p < 0.05; **p < 0.01; ***p < 0.001