Abstract

During the COVID-19 pandemic, SARS-CoV-2 variants drove large waves of infections, fueled by increased transmissibility and immune escape. Current models focus on changes in variant frequencies without linking them to underlying transmission mechanisms of intrinsic transmissibility and immune escape. We introduce a frame- work connecting variant dynamics to these mechanisms, showing how host population immunity interacts with viral transmissibility and immune escape to determine relative variant fitness. We advance a selective pressure metric that provides an early signal of epidemic growth using genetic data alone, crucial with current underreporting of cases. Additionally, we show that a latent immunity space model approximates immunological distances, offering insights into population susceptibility and immune evasion. These insights refine real-time forecasting and lay the groundwork for research into the interplay between viral genetics, immunity, and epidemic growth.