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. Here, USP18 is linked to COVID-19.