Modeling the Competitive Evolution and Large-scale Transmission Dynamics of SARS-CoV-2 and Emerging Viral Pathogens

A fundamental question in virology and epidemiology is how viral variants compete and evolve during large-scale transmission and what drives one variant to dominate—key to understanding pathogen emergence and mutation-driven fitness advantages. In this study, we address this by integrating epidemiological, clinical, and experimental data to examine the co-infection and competitive evolution of the earliest SARS-CoV-2 lineages, A and B, two key variants circulating in early 2020. To capture these dynamics, we developed the evolutionary-SIR-Seeding-Spreading (evoSSS) model, a holistic framework that integrates transmission, competition, and spatial bottlenecks. The model simulates viral competition across multiple scales, from intra-host replication to inter-host transmission and from regional outbreaks to global spread. It also predicts risks for other infectious pathogens, such as influenza and monkeypox, and clarifies the competitive interactions between SARS-CoV-2 and influenza viruses. This study provides valuable insights into viral competitive evolution and informs strategies for managing future pandemics.