Fig. 3

Differentially methylated genes in the PI3K/Akt pathway in severe versus mild COVID-19 patients. A Ingenuity Pathway Analysis (QIAGEN Ingenuity Pathway Analysis (IPA) version 01–21-03, Venlo, Netherlands) was performed demonstrating the interplay of differentially methylated genes (DMGs) with AKT1. Hypomethylated DMGs in severe versus mild COVID-19 within our dataset are depicted in orange; hypermethylated DMGs in severe versus mild COVID-19 are depicted in blue. Known relationships between genes as activators (black) and repressors (red) are shown, with direct interactions displayed as solid lines and indirect as dashed lines. Created with BioRender.com. B, C WGBS methylation analysis demonstrating hypomethylation of the AKT1 (B) and ISG15 (C) promoters (yellow rectangle) in individuals with severe COVID-19 as compared to mild COVID-19. Y-axis demonstrates percent methylation at a given CpG site (0–100%). Figure generated using the UCSC Genome Browser