One of the most serious viral outbreaks of the decade, infecting humans, originated from the city of Wuhan, China, by the end of December 2019, has left the world shaken up. It is the successor infection of severe acute respiratory syndrome coronavirus (SARS-CoV) named as SARS-CoV-2 causing a disease called as COVID-19 (Coronavirus disease-19). Being one of the most severe diseases in terms of transmission, this disease agitates the immune system of an individual quite disturbingly which at times leads to death, which is why it has become the need of the hour to step forward to extensively involve in understanding the genetics, pathogenesis, and immunopathology of SARS-CoV-2 in order to design drugs to treat or to design a vaccine to prevent. In this chapter, we have tried to review and summarize the studies done so far to understand the host–pathogen relationship and the host immune response during COVID-19 infection. One of the recent developments regarding the understanding of SARS-CoV-2 infection is the mechanism of immune evasion involved during the pathogenesis and cytokine storm syndrome during infection in the patient against which a drug called as Hydroxychloroquine has been designed. Comprehensively, we have tried to give an immunological insight into the SARS-CoV-2 infection in order to understand the possible outcome for any therapeutic advancement.