Conclusively, severe COVID-19 patients have (1) abnormal T cell function, (2) an inefficient clearance of infected/activated macrophages, (3) escalated viral replication/dissemination, and (4) activation of more macrophages by IL-18 and IFN-γ feed-forward loop, which results in multiple cytokine release, hemophagocytosis, coagulopathy, and ARDS. The gene discussed is IL18; the disease is COVID-19.