An allele-based model of coronavirus evolution under population immunity

Most epidemic models represent viral evolution at the level of whole strains, assigning transmissibility and immune escape directly to variants. However, in reality, mutations occur at specific genomic sites, and the epidemiological consequences of viral evolution depend on how these allele-level changes interact with population immunity.

We develop a compartmental model in which viral strains are defined by combinations of alleles across genomic sites, while transmission, immunity, waning, and mutation operate at the allele level. This framework allows evolutionary pressures acting on individual genomic components to propagate across multiple strains.

Even in a minimal system with two sites and two alleles per site, the model generates rich dynamics. Epidemic waves of an initially seeded strain produce an immune landscape that often favors genetically complementary strains. More generally, four mechanisms shape strain success: increases in prevalence of a strain due to increased transmissibility or immunity-avoidance of its underlying alleles, complementarity effects driven by population immunity, founder effects that indirectly favor the initially circulating strain, and adjacency effects associated with mutation pathways.

These results show that immune structure can redirect viral evolution in ways not captured by strain-based models and provide a simple framework linking viral genetics with epidemic dynamics.

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Simon C. P., Koopman J. S., Eisenberg M. C., Zaman L., Moreno M. A., & Polanco A. (2026). An allele-based model of coronavirus evolution under population immunity. medRxiv. https://doi.org/10.1101/2025.09.15.25335781

• supplementary material via medRxiv