Contact structure and population immunity shape the selective advantage of emerging variants.

Epidemics are shaped by the interplay between host and pathogen population characteristics, which are themselves intertwined. In particular, host behavior and immunity profile shape pathogen population structure by affecting both the likelihood of new variant emergence and its subsequent dynamics. Theoretical studies provided a fragmented description of this complex dynamical dependency, and the empirical evidence is limited. The SARS-CoV-2 pandemic presents an unprecedented opportunity to study the emergence of new variants. The relative growth of emerging variants over the resident ones, i.e., the selection coefficient, showed spatiotemporal variations that could be associated with population immunity and the mean and dispersion of contacts, which varied greatly according to epidemic intensity and human response. We first investigated the impact of these three features on the selection coefficient using a stochastic network-based model of new variant emergence, which incorporates tunable connectivity and heterogeneity. Results systematically chart the parameter space, uncover the boundaries of previously known associations, and quantify their strength. The mean number of contacts was positively associated with the selection coefficient, the effect being more robust for low immune-escape variants. The impact of immunity diminished as immunity increased. Importantly, greater contact dispersion slowed down the spread of variants lacking immune escape, but this effect quickly reversed once immune escape became non-zero. We then analysed the emergence of the SARS-CoV-2 Alpha variant in the United States at the state level, examining the association of the selection coefficient with the three population features under study, reconstructed from serological, vaccination, and contact survey data. Regression analyses revealed a strong effect of population characteristics. Comparing empirical trends with model predictions showed consistency and suggested that the selection coefficient was more affected by contact statistics than by immunity. These results shed light on how human population structure mediates variant dynamics and help interpret the heterogeneity observed in variant emergence.