ISG15 and COVID-19: Interestingly, the upregulation of the inflammatory genes FOS, JUNB, the downregulation of the interferon-induced genes, including ISG15, IFI6, IFI44, IFIT3, IFI44L, and suppression of the interferon regulatory factors, including (IRF7) driven by M protein were implicated as the key players for this association, suggesting that the molecular signature of SARS-CoV-2 M protein-reactive CD4+ TCLs is characterized by suppression of the same interferon pathways seen in the transcriptional profile of severe COVID-19.