The unprecedented COVID-19 crisis has led to a worldwide effort to rapidly characterize the virology of SARS-CoV-2, while mitigating further spread of this deadly pathogen. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. This talk will provide an overview of the pathophysiology of SARS-CoV-2 infection. I will describe its interaction with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression that provided useful insights in the successful development of vaccines and booster strategies.