Evolution of new variants of SARS-CoV-2 during the pandemic: mutation-limited or selection-limited?

The recent SARS-CoV-2 pandemic has witnessed the emergence of various virus variants. While the phenomenon of immunity-evading variants is known in other viruses like influenza, there is limited understanding of the ecological and evolutionary processes involved in this succession. Due to the availability of large-scale epidemiological data collected and shared publicly during the Covid-19 pandemic, it becomes possible to explore evolutionary questions that also have implications for public health. We propose multiple alternative hypotheses regarding the origin and spread of these variants and evaluate them based on epidemiological data. Our analysis indicates that the invasion of novel variants is primarily limited by selection rather than mutation. Moreover, the repeated waves observed during the pandemic are not solely caused by the emergence of new variants. Instead, there is a significant overlap between conditions that lead to a wave and those that favor the selection of partially immune-evading variants. This association may contribute to the rise of a new wave alongside the invasion of a new variant. However, the association is not strong enough to support a causal role of the new variant. The dynamic interplay between epidemiological processes and selection on viral variants carries important implications for public health and can guide future policies aimed at effectively controlling infectious epidemics.