SARS-CoV-2 before and after Omicron: two different viruses and two different diseases?

Abstract For the first time in the history of medicine, it has been possible to describe—after a spillover—the evolution of a new human virus spreading in a non-immune population. This allowed not only to observe the subsequent emersion of variants endowed with features providing the virus with an evolutionary advantage, but also the shift of the pathways of virus replication and the acquisition of immunoevasive features. These characteristics had a remarkable influence on the diffusion of the SARS-CoV-2 and on the clinical presentation and prognosis of COVID-19, aspects that are described and commented in this review.