The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to wreak havoc around the world. Significant global efforts have been made to understand the disease immunopathogenesis, which permitted the development of vaccines and effective therapies. This talk will provide an overview of the pathophysiology of SARS-CoV-2 infection. I will also describe how mutations in the emerging variants of concern and vaccination impact the immune response, which provides important insights into the therapeutic management of diseases caused by these variants.Â