Matthijs Meijers, Denis Ruchnewitz, Jan Eberhardt, Marta Łuksza, Michael Lässig

The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross- immunity induced by previous infections or vaccinations. How this functional variation shapes global evolu- tion has remained unclear. Here, we establish a predictive fitness model for SARS-CoV-2 that integrates antigenic and intrinsic selection. 

The model is informed by tracking of time-resolved sequence data, epide- miological records, and cross-neutralization data of viral variants. Our inference shows that immune pres- sure, including contributions of vaccinations and previous infections, has become the dominant force driving the recent evolution of SARS-CoV-2. The fitness model can serve continued surveillance in two ways. First, it successfully predicts the short-term evolution of circulating strains and flags emerging variants likely to displace the previously predominant variant. Second, it predicts likely antigenic profiles of successful escape variants prior to their emergence.