Our study found that the high expression of IFN-β in COVID-19 patients induced an increase in ISG15 and a high expression of IFIT1 (ISG56), the main subclass of ISG proteins with broad-spectrum antiviral activity, which may be the antiviral immune mechanism induced by SARS-CoV-2 infection [13,58,59]. This evidence concerns the gene ISG15 and COVID-19.