Consistently, genes (e.g., ISG15, IFITM1/2/3, OAS3 and IFIT1/2/3) associated with the IFN-response pathway, especially for IFN-I response (Supplementary Fig. 7b), were significantly upregulated in COVID-19 associated acute necrotizing encephalopathy compared with healthy donors and other COVID-19 groups (Fig. 5c). The gene discussed is ISG15; the disease is COVID-19.