Evolutionary Mechanisms of the Emergence of the Variants of Concern of SARS-CoV-2

The evolutionary origin of the variants of concern (VOCs) of SARS-CoV-2, characterized by a large number of new substitutions and strong changes in virulence and transmission rate, is intensely debated. The leading explanation in the literature is a chronic infection in immunocompromised individuals, where the virus evolves before returning into the main population. The present article reviews less-investigated hypotheses of VOC emergence with transmission between acutely infected hosts, with a focus on the mathematical models of stochastic evolution that have proved to be useful for other viruses, such as HIV and influenza virus. The central message is that understanding the acting factors of VOC evolution requires the framework of stochastic multi-locus evolution models, and that alternative hypotheses can be effectively verified by fitting results of computer simulation to empirical data.