Abstract

SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic – especially that of immune escape – remains a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility easily rise to high frequency, whereas partial immune escape, on its own, often fails to do so. However, when these phenotypes are combined, enhanced transmissibility can carry the variant to high frequency, at which point partial immune escape may limit the ability of vaccination to control the epidemic. Our findings suggest that moderate immune escape poses a low risk unless combined with a substantial increase in transmissibility.Funding: MB and BPT were supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI128344. RK, ML and WPH were supported by the U.S. National Cancer Institute SeroNet cooperative agreement U01CA261277.Declaration of Interests: RK discloses consulting fees from Partners In Health and the PanAmerican Health Organization. ML received funding through his institution from US CDC, NIH, and UK National Institute for Health Research, and Pfizer, and consulting fees or honoraria from Merck,Sanofi Pasteur, Janssen, and Bristol Myers Squibb. He is a member of the Scientific Advisory Board for CEPI, the Coalition for Epidemic Preparedness Innovations. WPH serves on the Advisory Board of Biobot Analytics and has received compensation for expert witness testimony on the course of the SARS-CoV-2 pandemic. All others have nothing to disclose.

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