Genes comprising DMRs between patients with COVID-19 and healthy pre-pandemic controls include IFN-stimulated genes (ISGs), with well-recognized antiviral activity such as IFI27 and OAS2. Differential methylation of type I IFN pathway genes in specific leukocyte subsets is associated with autoimmune disorders including Sjogren’s syndrome, Lupus, Grave’s disease, and rheumatoid arthritis [51–55], indicating a possible role for ISG methylation in the dysregulation of inflammatory processes, and autoimmunity as a potential contributor to COVID-19 pathogenesis [56, 57]. Here, IFI27 is linked to rheumatoid arthritis.