Assessing the risk of vaccine-driven virulence evolution in SARS-CoV-2

Ian F. Miller, C. Jessica E. Metcalf

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The evolution of SARS-CoV-2 virulence, or lethality, threatens to exacerbate the burden of COVID-19 on society. How might COVID-19 vaccines alter selection for increased SARS-CoV-2 virulence? Framing current evidence surrounding SARS-CoV-2 biology and COVID-19 vaccines in the context of evolutionary theory indicates that prospects for virulence evolution remain uncertain. However, differential effects of vaccinal immunity on transmission and disease severity between respiratory compartments could select for increased virulence. To bound expectations for this outcome, we analyse an evo-epidemiological model. Synthesizing model predictions with vaccine efficacy data, we conclude that while vaccine-driven virulence remains a theoretical possibility, the risk is low if vaccines provide sustained robust protection against infection. Furthermore, we found that any increases in transmission concomitant with increases in virulence would be unlikely to threaten prospects for herd immunity in a highly immunized population. Given that virulence evolution would nevertheless impact unvaccinated individuals and populations with low vaccination rates, it is important to achieve high vaccination rates worldwide and ensure that vaccinal immunity provides robust protection against both infection and disease, potentially through the use of booster doses.

Original languageEnglish (US)
Article number211021
JournalRoyal Society Open Science
Issue number1
StatePublished - 2022

All Science Journal Classification (ASJC) codes

  • General


  • COVID-19
  • vaccine
  • virulence evolution


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