ISG15 and COVID-19: Indeed, many canonical IFN-stimulating genes (ISGs), including ISG15, IFITM1, IFITM3, MX1, IRF7, IFI27, etc., were expressed at higher levels in COVID-19 patients than controls, while the genes associated with neutrophil activation, including S100A8, S100A9, S100A12, CLU, RNASE2, etc., were expressed at higher levels in severe COVID-19 than mild COVID-19 and controls (Fig. 2e).