text: Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID 19 a review of the phases of illness and therapeutic agents Coronavirus disease 2019 COVID 19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 SARS CoV 2 previously named 2019 nCov a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th 2020 Severe manifestations of COVID 19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage We reviewed published literature between January 1st 2000 and June 30th 2020 excluding articles focusing on pediatric or obstetric population with a focus on virus host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome CRS COVID 19 illness encompasses three main phases In phase 1 SARS CoV 2 binds with angiotensin converting enzyme ACE 2 receptor on alveolar macrophages and epithelial cells triggering toll like receptor TLR mediated nuclear factor kappa light chain enhancer of activated B cells NF ƙB signaling It effectively blunts an early IFN response allowing unchecked viral replication Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms persistent fever and hemodynamic instability Important cytokines involved in this phase are interleukin IL 6 IL 1β and tumor necrosis factor TNF α This is typically followed by a recovery phase with production of antibodies against the virus We summarize published data regarding virus host interactions key immunological mechanisms responsible for virus associated CRS and potential opportunities for therapeutic interventions Evidence regarding SARS CoV 2 epidemiology and pathogenesis is rapidly evolving A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID 19 is imperative to identify novel drug targets and other therapeutic interventions 