Extended Data Fig. 3: Altered expression of iron-response gene-sets in COVID-19 severity groups over time.

a, Distribution of log₂FC values across 324 measured genes with high-quality conserved iron-response elements (IRE_HQ) in their 3’ or 5’ UTR, derived from the whole-blood transcriptome comparison of COVID-19 severity groups (A-E) and HC over successive time windows. b, Distribution at day 0-14 from a, compared to corresponding distribution of log₂FC values across 150 measured proteins in the IRE_HQ gene set, taken from matched samples within the same time window. Samples from patients in groups D and E, and groups A and B, were analyzed together relative to HC to improve sample sizes (n(HC)=7, n(A_B)=7, n(C)=5, n(D_E)=9). c, Correlation of log₂FC values from the transcriptional comparison of group E patients and HC, and the protein level comparison of groups D+E and HC, at day 0-14. Pearson’s correlation coefficient and p-value shown. d, Distribution of log₂FC values across 60 measured iron homeostasis genes, derived from the whole blood transcriptome comparison of COVID-19 severity groups and HC over successive time windows, GSEA p-value from gene-set enrichment analysis shown. e, Heat map showing log₂FC of each gene in more detail. Significantly differentially expressed genes (P_FDR<0.1, abs(log₂FC) >0.5) are indicated with asterisks: * P_FDR<0.1, ** P_FDR<0.05, ***P_FDR<0.005. f, Change in expression of master regulator of the antioxidant response, NFE2L2 (encoding NRF2), over time and across severity groups. Gray bar indicates IQR of the interquartile range of the HCs. FDR adjusted p-values from linear model fit: *p<0.1, **p<0.05, ***p<0.005. Boxplots show minimum, 25^th percentile, median, 75^th percentile and maximum, and outliers beyond 1.5 times the interquartile range.