Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals

Haogao Gu, Ahmed Abdul Quadeer, Pavithra Krishnan, Daisy Y. M. Ng, Lydia D. J. Chang, Gigi Y. Z. Liu, Samuel M. S. Cheng, Tommy T. Y. Lam, Malik Peiris, Matthew R. McKay and Leo L. M. Poon ()
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Haogao Gu: The University of Hong Kong
Ahmed Abdul Quadeer: The Hong Kong University of Science and Technology
Pavithra Krishnan: The University of Hong Kong
Daisy Y. M. Ng: The University of Hong Kong
Lydia D. J. Chang: The University of Hong Kong
Gigi Y. Z. Liu: The University of Hong Kong
Samuel M. S. Cheng: The University of Hong Kong
Tommy T. Y. Lam: The University of Hong Kong
Malik Peiris: The University of Hong Kong
Matthew R. McKay: The Hong Kong University of Science and Technology
Leo L. M. Poon: The University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification. Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.

Date: 2023
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DOI: 10.1038/s41467-023-37468-y

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