Anti-viral ISGs including, MAVS, OAS1, OAS2, OAS3, BST2, DHX58, IFNAR2, IRF2BP1, IRF4, MX1, PARP12, SAMD9L, SAMHD1, STAT2, TDR07, TRIM14, TRIM32, USP18, ZBP1, IRF4 and STAT showed marked downregulation in severe COVID-19. The gene discussed is IRF4; the disease is COVID-19.