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  • Open Access

Eco-Evolutionary Constraints for the Endemicity of Rapidly Evolving Viruses

David Soriano-Paños*

  • *Contact author: sorianopanos@gmail.com

PRX Life 3, 043001 – Published 2 October, 2025

DOI: https://doi.org/10.1103/43bd-hxhl

Abstract

Antigenic escape constitutes the main mechanism allowing rapidly evolving viruses to achieve endemicity. Beyond granting immune escape, empirical evidence also suggests that mutations of viruses might increase their interhost infectiousness. While both mechanisms are well-studied individually, their combined effects on viral endemicity remain to be explored. Here we propose a minimal eco-evolutionary framework to simulate epidemic outbreaks generated by pathogens evolving both their infectiousness and immune escape. Our results reveal that the main driver of viral evolution shifts over time: from intrinsic selection for infectiousness at early stages of the outbreak to antigenic diversification in the transition to the endemic phase. We find that the evolution in both traits during the first epidemic wave plays a critical role in determining long-term viral persistence. Evolution in infectiousness enhances the endemicity of viruses, especially in viruses with lower baseline infectiousness due to the longer duration of their first epidemic wave. Likewise, control policies flattening epidemic curves might increase viral endemicity as a result of the greater antigenic diversity generated in the prolonged epidemic waves. Our results thus prove that the long-term behavior of epidemic trajectories hinges on the complex interplay between both evolutionary pathways and the underlying contagion dynamics.

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References (68)

  1. A. Moya, E. C. Holmes, and F. González-Candelas, The population genetics and evolutionary epidemiology of rna viruses, Nat. Rev. Microbiol. 2, 279 (2004).
  2. J. D. Gass Jr, R. J. Dusek, J. S. Hall, G. T. Hallgrimsson, H. P. Halldórsson, S. R. Vignisson, S. B. Ragnarsdottir, J. E. Jónsson, S. Krauss, S.-S. Wong et al., Global dissemination of influenza a virus is driven by wild bird migration through arctic and subarctic zones, Mol. Ecol. 32, 198 (2023).
  3. D. G. Streicker, A. S. Turmelle, M. J. Vonhof, I. V. Kuzmin, G. F. McCracken, and C. E. Rupprecht, Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats, Science 329, 676 (2010).
  4. Z. Chen, A. S. Azman, X. Chen, J. Zou, Y. Tian, R. Sun, X. Xu, Y. Wu, W. Lu, S. Ge et al., Global landscape of SARS-CoV-2 genomic surveillance and data sharing, Nat. Genet. 54, 499 (2022).
  5. M. J. Keeling and P. Rohani, Modeling Infectious Diseases in Humans and Animals (Princeton University Press, Princeton, NJ, 2011).
  6. A. P. Galvani, Epidemiology meets evolutionary ecology, Trends Ecol. Evolut. 18, 132 (2003).
  7. D. N. Makau, S. Lycett, M. Michalska-Smith, I. A. Paploski, M. C.-J. Cheeran, M. E. Craft, R. R. Kao, D. C. Schroeder, A. Doeschl-Wilson, and K. Van der Waal, Ecological and evolutionary dynamics of multi-strain RNA viruses, Nature Ecol. Evolution 6, 1414 (2022).
  8. A. M. Carabelli, T. P. Peacock, L. G. Thorne, W. T. Harvey, J. Hughes, S. J. Peacock, W. S. Barclay, T. I. De Silva, G. J. Towers, and D. L. Robertson, SARS-CoV-2 variant biology: immune escape, transmission and fitness, Nat. Rev. Microbiol. 21, 162 (2023).
  9. D. J. Smith, A. S. Lapedes, J. C. De Jong, T. M. Bestebroer, G. F. Rimmelzwaan, A. D. Osterhaus, and R. A. Fouchier, Mapping the antigenic and genetic evolution of influenza virus, Science 305, 371 (2004).
  10. A. Tuekprakhon, R. Nutalai, A. Dijokaite-Guraliuc, D. Zhou, H. M. Ginn, M. Selvaraj, C. Liu, A. J. Mentzer, P. Supasa, H. M. Duyvesteyn et al., Antibody escape of SARS-CoV-2 omicron ba. 4 and ba. 5 from vaccine and ba. 1 serum, Cell 185, 2422 (2022).
  11. C. E. Van de Sandt, J. H. Kreijtz, and G. F. Rimmelzwaan, Evasion of influenza a viruses from innate and adaptive immune responses, Viruses 4, 1438 (2012).
  12. B. J. Williams, G. St-Onge, and L. Hébert-Dufresne, Localization, epidemic transitions, and unpredictability of multistrain epidemics with an underlying genotype network, PLoS Comput. Biol. 17, e1008606 (2021).
  13. B. J. Williams, C. B. Ogbunugafor, B. M. Althouse, and L. Hébert-Dufresne, Immunity-induced criticality of the genotype network of influenza A (H3N2) hemagglutinin, PNAS nexus 1, pgac143 (2022).
  14. Y. Nie, X. Zhong, T. Lin, and W. Wang, Pathogen diversity in meta-population networks, Chaos Solitons Fractals 166, 112909 (2023).
  15. J. R. Gog and B. T. Grenfell, Dynamics and selection of many-strain pathogens, Proc. Natl. Acad. Sci. 99, 17209 (2002).
  16. K. Koelle, M. Kamradt, and M. Pascual, Understanding the dynamics of rapidly evolving pathogens through modeling the tempo of antigenic change: influenza as a case study, Epidemics 1, 129 (2009).
  17. I. Atienza-Diez and L. F. Seoane, Long-and short-term effects of cross-immunity in epidemic dynamics, Chaos Solitons Fractals 174, 113800 (2023).
  18. L. Yan, R. A. Neher, and B. I. Shraiman, Phylodynamic theory of persistence, extinction and speciation of rapidly adapting pathogens, Elife 8, e44205 (2019).
  19. I. M. Rouzine and G. Rozhnova, Antigenic evolution of viruses in host populations, PLoS Pathog. 14, e1007291 (2018).
  20. J. Marchi, M. Lässig, A. M. Walczak, and T. Mora, Antigenic waves of virus–immune coevolution, Proc. Natl. Acad. Sci. 118, e2103398118 (2021).
  21. A. D. Stewart, J. M. Logsdon, and S. E. Kelley, An empirical study of the evolution of virulence under both horizontal and vertical transmission, Evolution 59, 730 (2005).
  22. A. C. Brault, C. Y. Huang, S. A. Langevin, R. M. Kinney, R. A. Bowen, W. N. Ramey, N. A. Panella, E. C. Holmes, A. M. Powers, and B. R. Miller, A single positively selected west nile viral mutation confers increased virogenesis in american crows, Nat. Genet. 39, 1162 (2007).
  23. T. W. Berngruber, R. Froissart, M. Choisy, and S. Gandon, Evolution of virulence in emerging epidemics, PLoS Pathogens 9, e1003209 (2013).
  24. B. A. Walther and P. W. Ewald, Pathogen survival in the external environment and the evolution of virulence, Biol. Rev. 79, 849 (2004).
  25. X. Zhang, Z. Ruan, M. Zheng, J. Zhou, S. Boccaletti, and B. Barzel, Epidemic spreading under mutually independent intra-and inter-host pathogen evolution, Nat. Commun. 13, 6218 (2022).
  26. C. M. Saad-Roy, N. S. Wingreen, S. A. Levin, and B. T. Grenfell, Dynamics in a simple evolutionary-epidemiological model for the evolution of an initial asymptomatic infection stage, Proc. Natl. Acad. Sci. USA 117, 11541 (2020).
  27. S. T. Abedon, T. D. Herschler, and D. Stopar, Bacteriophage latent-period evolution as a response to resource availability, Appl. Environmental Microbiol. 67, 4233 (2001).
  28. C. van Oosterhout, N. Hall, H. Ly, and K. M. Tyler, COVID-19 evolution during the pandemic–implications of new SARS-CoV-2 variants on disease control and public health policies, Virulence 12, 507 (2021).
  29. J. L. Americo, P. L. Earl, and B. Moss, Virulence differences of mpox (monkeypox) virus clades I, IIa, and IIb. 1 in a small animal model, Proc. Natl. Acad. Sci. USA 120, e2220415120 (2023).
  30. P. V. Markov, M. Ghafari, M. Beer, K. Lythgoe, P. Simmonds, N. I. Stilianakis, and A. Katzourakis, The evolution of SARS-CoV-2, Nature Reviews Microbiology 21, 361 (2023).
  31. K. Koelle, M. A. Martin, R. Antia, B. Lopman, and N. E. Dean, The changing epidemiology of SARS-CoV-2, Science 375, 1116 (2022).
  32. V. Chardès, A. Mazzolini, T. Mora, and A. M. Walczak, Evolutionary stability of antigenically escaping viruses, Proc. Natl. Acad. Sci. USA 120, e2307712120 (2023).
  33. A. Sasaki, S. Lion, and M. Boots, Antigenic escape selects for the evolution of higher pathogen transmission and virulence, Nat. Ecol. Evolution 6, 51 (2022).
  34. L. E. Cohen, D. J. Spiro, and C. Viboud, Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations, PLoS Pathog. 18, e1010591 (2022).
  35. J. S. Lavine, O. N. Bjornstad, and R. Antia, Immunological characteristics govern the transition of covid-19 to endemicity, Science 371, 741 (2021).
  36. R. Antia and M. E. Halloran, Transition to endemicity: Understanding covid-19, Immunity 54, 2172 (2021).
  37. J. Wallinga and P. Teunis, Different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures, Am. J. Epidemiol. 160, 509 (2004).
  38. S. Alizon, Transmission-recovery trade-offs to study parasite evolution, Am. Nat. 172, E113 (2008).
  39. M. Turkyilmazoglu, Explicit formulae for the peak time of an epidemic from the sir model, Physica D 422, 132902 (2021).
  40. M. Biancolella, V. L. Colona, R. Mehrian-Shai, J. L. Watt, L. Luzzatto, G. Novelli, and J. K. Reichardt, Covid-19 2022 update: transition of the pandemic to the endemic phase, Human Genomics 16, 19 (2022).
  41. I. S. Novella, E. A. Duarte, S. F. Elena, A. Moya, E. Domingo, and J. J. Holland, Exponential increases of rna virus fitness during large population transmissions., Proc. Natl. Acad. Sci. USA 92, 5841 (1995).
  42. L. S. Tsimring, H. Levine, and D. A. Kessler, Rna virus evolution via a fitness-space model, Phys. Rev. Lett. 76, 4440 (1996).
  43. J. Venegas-Ortiz, R. J. Allen, and M. R. Evans, Speed of invasion of an expanding population by a horizontally transmitted trait, Genetics 196, 497 (2014).
  44. M. Meijers, D. Ruchnewitz, J. Eberhardt, M. Łuksza, and M. Lässig, Population immunity predicts evolutionary trajectories of SARS-CoV-2, Cell 186, 5151 (2023).
  45. T. L. Parsons, B. M. Bolker, J. Dushoff, and D. J. Earn, The probability of epidemic burnout in the stochastic sir model with vital dynamics, Proc. Natl. Acad. Sci. USA 121, e2313708120 (2024).
  46. O. A. van Herwaarden, Stochastic epidemics: the probability of extinction of an infectious disease at the end of a major outbreak, J. Math. Biol. 35, 793 (1997).
  47. N. Perra, Non-pharmaceutical interventions during the covid-19 pandemic: A review, Phys. Rep. 913, 1 (2021).
  48. N. Haug, L. Geyrhofer, A. Londei, E. Dervic, A. Desvars-Larrive, V. Loreto, B. Pinior, S. Thurner, and P. Klimek, Ranking the effectiveness of worldwide covid-19 government interventions, Nat. Human Behav. 4, 1303 (2020).
  49. B. Ashby, C. A. Smith, and R. N. Thompson, Non-pharmaceutical interventions and the emergence of pathogen variants, Evolution, Med, Public Health 11, 80 (2023).
  50. Y. Gurevich, Y. Ram, and L. Hadany, Modeling the evolution of SARS-CoV-2 under non-pharmaceutical interventions and testing, Evolution, Med., Public Health 10, 179 (2022).
  51. R. E. Baker, S. W. Park, W. Yang, G. A. Vecchi, C. J. E. Metcalf, and B. T. Grenfell, The impact of covid-19 nonpharmaceutical interventions on the future dynamics of endemic infections, Proc. Natl. Acad. Sci. USA 117, 30547 (2020).
  52. M. Aguilar-Bretones, R. A. Fouchier, M. P. Koopmans, G. P. van Nierop et al., Impact of antigenic evolution and original antigenic sin on SARS-CoV-2 immunity, J. Clin. Invest. 133 (2023).
  53. N. L. Miller, T. Clark, R. Raman, and R. Sasisekharan, An antigenic space framework for understanding antibody escape of SARS-CoV-2 variants, Viruses 13, 2009 (2021).
  54. I. M. Rouzine and G. Rozhnova, Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies, Commun. Med. 3, 86 (2023).
  55. S. Wright, Isolation by distance, Genetics 28, 114 (1943).
  56. S. W. Attwood, S. C. Hill, D. M. Aanensen, T. R. Connor, and O. G. Pybus, Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic, Nat. Rev. Genet. 23, 547 (2022).
  57. G. Hess, Disease in metapopulation models: implications for conservation, Ecology 77, 1617 (1996).
  58. L. Goiriz, R. Ruiz, Ò. Garibo-i Orts, J. A. Conejero, and G. Rodrigo, A variant-dependent molecular clock with anomalous diffusion models SARS-CoV-2 evolution in humans, Proc. Natl. Acad. Sci. 120, e2303578120 (2023).
  59. S. Manrubia, J. A. Cuesta, J. Aguirre, S. E. Ahnert, L. Altenberg, A. V. Cano, P. Catalán, R. Diaz-Uriarte, S. F. Elena, J. A. García-Martín et al., From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics, Phys. Life Rev. 38, 55 (2021).
  60. D. H. Goldhill and P. E. Turner, The evolution of life history trade-offs in viruses, Curr. Opin. Virol. 8, 79 (2014).
  61. M. A. Acevedo, F. P. Dillemuth, A. J. Flick, M. J. Faldyn, and B. D. Elderd, Virulence-driven trade-offs in disease transmission: A meta-analysis, Evolution 73, 636 (2019).
  62. S. Alizon, A. Hurford, N. Mideo, and M. Van Baalen, Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future, J. Evolutionary Biol. 22, 245 (2009).
  63. E. E. Bendall, A. P. Callear, A. Getz, K. Goforth, D. Edwards, A. S. Monto, E. T. Martin, and A. S. Lauring, Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants, Nat. Commun. 14, 272 (2023).
  64. A. Gómez-Carballa, J. Pardo-Seco, X. Bello, F. Martinón-Torres, and A. Salas, Superspreading in the emergence of covid-19 variants, Trends Genet. 37, 1069 (2021).
  65. S. Harari, M. Tahor, N. Rutsinsky, S. Meijer, D. Miller, O. Henig, O. Halutz, K. Levytskyi, R. Ben-Ami, A. Adler et al., Drivers of adaptive evolution during chronic SARS-CoV-2 infections, Nat. Med. 28, 1501 (2022).
  66. N. Blot, C. Brooks, D. W. Swartz, E. Abdelaleem, M. Garic, A. Iglesias-Ramas, M. Pasek, T. Mora, and A. M. Walczak, How host mobility patterns shape antigenic escape during viral-immune coevolution, PRX Life 3, 023011 (2025).
  67. https://github.com/sorianopanos/ecoevolutionary
  68. R. M. Anderson and R. M. May, Coevolution of hosts and parasites, Parasitology 85, 411 (1982).

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