Coronavirus disease 2019 or COVID-19, caused by the novel human coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019, in the city of Wuhan, Hubei province, China. Unfortunately, despite many efforts to find cures for SARS-CoV-2 disease, still the management of severe cases remains challenging. In severe forms of COVID-19, proinflammatory cytokines are notably elevated (3) and reminiscent of the secondary hemophagocytic lymphohistiocytosis (HLH). According to many studies, immune imbalance and an uncontrolled massive release of inflammatory cytokines have a significant role in COVID-19 severity and ARDS pathophysiology. Accordingly, targeting the over-activated immune system to prevent tissue damage is now one of the most noticed possible strategies to manage severe COVID-19 cases. In the present study, we reviewed studies and clinical trials conducted in this regard.