ISG15 and COVID-19: Across the 19 donors, two clusters of effector CD4+ T cells were present in higher proportions in both COVID-19 and HIV-1+ patients relative to healthy controls, but especially frequent in COVID-19 patients: IFN-I+ CD4+ T cells, expressing high levels of IFN-I-stimulated genes ISG15 and IFIT3, as well as IL7R, all of which are reported to be upregulated by IFNβ in CD4+ T cells (Hoe et al., 2010); and cytotoxic CD4+ T cells, expressing cytotoxic genes GZMH, GNLY, NKG7, PRF1, and GZMB (Figures 5C, D).