Most downregulated genes in the severe COVID-19 cohort, including ISG15, OAS1, SAMD9L, and IFIT1, are associated with antiviral response pathways, and immune response-related pathways and processes were suppressed in individuals with severe COVID-19, suggesting an impaired upper-respiratory airway immune response (Figures 2(c) and 3(e)–3(h), Supplementary 5). This evidence concerns the gene ISG15 and COVID-19.