Interferon Gamma Receptor 1 (IFNGR1), Interferon Alpha and Beta Receptor Subunit 1 (IFNAR1), Interleukin 1 Receptor (INFLR1), and ISGs like Interferon-Induced Transmembrane Protein 3 (IFITM3), ISG15 Ubiquitin-Like Modifier (ISG15), Tryptophanyl-tRNA Synthetase (WARS), Myxovirus Resistance Proteins 1 and 2 (MX1 and MX2), Interferon Gamma Inducible Protein 16 (IFI16), and Oligoadenylate Synthetases 1, 2, and 3 (OAS1, OAS2, OAS3), which are pivotal in interferon signaling and antiviral defense, increased markedly in moderate COVID-19 patients. This evidence concerns the gene ISG15 and COVID-19.