Fig. 3

NF-kB is associated with the regulation of the transcriptional alterations of IL2-AIS genes in COVID-19 patients. A Enrichment of IL2-AIS constituent genes in each multi-modal gene expression component reported in the COMBAT study [5]. Each dot represents a disease-associated gene expression component identified in the COMBAT study. Dot sizes represent the number of shared genes between the respective component and the 41 IL2-AIS constituent genes. The top 50 components are shown, ranked by their odds ratios of enrichment (x-axis). Colours depict cluster membership as reported in the COMBAT study. Components in the same cluster are associated with diseases in a similar way. Cluster 3 is associated with all severity groups of COVID-19. The three components with odds ratio ⩾ 5 are highlighted with a dashed blacked box. B Component 187 loading scores are negatively correlated with the differential expression induced by IL-2 immunotherapy, as reported in the DILfrequency cohort. Of the 1,419 genes included in Component 187, 69 are also present in the target transcriptional panel used in the DILfrequency study [4]. The effects of IL-2 immunotherapy and SARS-CoV-2 infection on the induction of these genes are compared by correlating component gene loading score (y-axis) with log₂ fold change (x-axis) in the CD8 population. The positive and negative values in Component 187 loading scores represent the upregulation and downregulation of the corresponding gene, respectively, after SARS-CoV-2 infection. Each dot represents a gene. Larger dots represent genes with FDR-adjusted P values < 0.01 in the DILfrequency dataset. C Correlation between the IL2-AIS score and the Component 187 sample loading score. Each dot represents a participant in the COMBAT cohort and colours depict the different participant groups. D STRING [17] protein interaction network of top 50 genes in Component 187. Each node represents a gene. Node colours represent Component 187 gene loading scores. IL2-AIS genes are labelled in bold text with directions of IL-2-induced differential expression shown in arrows. Each edge represents experimental or inferred protein–protein interaction between two genes. Edge widths and colours represent interaction scores, with thicker lines and darker colours representing higher scores. IL2-AIS, anti-inflammatory gene expression signature induced by low-dose IL-2 immunotherapy