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COVID-19 has killed millions globally. SARS-CoV-2, a virus that belongs to the Coronaviridae family, causes COVID-19. Literature suggests that COVID-19-related illness, severity, and mortality are caused by cytokine storm (CS), a systemic inflammatory response. In CS, the immune system produces elevated proinflammatory cytokines’ levels, causing multiorgan dysfunction and death. In some patients, COVID-19 results in the onset of acute respiratory distress syndrome, which demands early detection and treatment or can be fatal. CS has been associated with many other illnesses as well. In this chapter, we provide a succinct account of the key events involved in the emergence of CS upon SARS-CoV-2 infection. We also describe the role of key proinflammatory cytokines that result in the abnormal immune response by the host. This chapter includes different therapeutic interventions currently being used in an …