Collectively, our findings characterize ACE2 and IL-6 genes as non-ISGs responding differently to inflammatory and IFN signaling, and their epigenetic properties may serve as biomarkers to predict COVID-19 susceptibility in vertebrates longitudinally and partially explain COVID-19 inequality in people of different subgroups [20,30,31,32,33]. This evidence concerns the gene IFNA1 and COVID-19.