Integrated framework to study genomic surveillance of selective sweeps in multivariants dynamics.

Pandemics often involve complex transmission dynamics in which epidemiological surveillance is essential but not sufficient for containment, as resurgence may be driven by emerging or imported variants. Rapidly evolving pathogens produce complex disease dynamics driven by emerging variants often differing in their transmissibility, immune escape, and cross-infection. These processes influence individuals' immune life histories, producing highly dynamic immune landscapes that modulate the emergence and dominance of novel variants. We develop an integrated modeling framework that couples multivariant mean-field epidemic modeling with a mechanistic genomic dominance model and a probabilistic surveillance model. This study examines how variant emergence timing, infectiousness advantage, and cross-infection jointly shape epidemic trajectories, immune landscapes, and genomic composition. Our results demonstrate that the dominance dynamics of cocirculating variants correspond to a selective sweep characterized by a system of multilogistic equations driven by population immunity. Moreover, we show that the detection time of newly introduced variants can be accelerated or delayed depending on their emergence conditions and the prevailing variant landscape. Finally, we demonstrate that the effectiveness of response strategies depends critically on the evolving genomic composition of the outbreak, highlighting trade-offs between surveillance sensitivity and intervention timing. We validate our framework by jointly fitting epidemiological and genomic data from the spread of the Ancestral, Alpha, Gamma, and Delta variants in the United States, Denmark, the United Kingdom, and Canada. The results provide a quantitative foundation for linking epidemic dynamics, genomic surveillance, and immune life histories, advancing the development of genomic epidemiology for multivariant outbreaks.