Speaker
Description
The ongoing evolution of SARS-CoV-2, marked by the continued emergence of highly divergent variants with increased transmissibility and immune evasion, underscores the importance of understanding viral evolutionary dynamics, particularly in relation to understanding the evolutionary processes involved in the emergence of these variants. We previously developed a method to identify persistent SARS-CoV-2 infections from genomic sequence data, identified through the Office for National Statistics Covid Infection Survey (1). Here we expanded our dataset, identifying 576 persistently infected individuals, with 27 infections lasting over three months and the longest infection nearly a year. We estimated genome-wide, synonymous, and nonsynonymous virus evolutionary rates within these individuals, accounting for noise-driven changes in mutation frequencies, and compared these to between-host rates of evolution (2). We found significant variation in evolutionary rates among persistent infections, primarily driven by differences in nonsynonymous rates, and a strong signal for accelerated divergence rate in the spike protein's receptor binding domain. In addition, we explored the within-host genetic diversity of the virus over the course of infection, identifying some genomic regions, such as ORF6, that were under strong purifying selection, but other regions, such as E and ORF8, that were under strong directional selection. We did not find any evidence that host factors such as age, sex, vaccination status, prior infection, or virus lineage strongly associate with evolutionary rates in persistent infections, with the exception of a few older male individuals who had noticeably higher rates of evolution. This study provides valuable insights into the evolutionary dynamics of SARS-CoV-2 at the within-host level and its likely impact on the evolutionary trajectory of the virus at the between-host level, improving our understanding of viral adaptation and possible mechanisms behind the generation of new variants.
- Ghafari et al. Nature 2024 (in press) DOI: 10.1038/s41586-024-07029-4
- Lythgoe et al. Proc. Roy. Soc. B 2023 DOI: 10.1098/rspb.2023.1284
