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

Author

Listed:
  • 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
    Hong Kong Science and Technology Park
    Hong Kong Science and Technology Park)

  • Malik Peiris

    (The University of Hong Kong
    Hong Kong Science and Technology Park
    The University of Hong Kong)

  • Matthew R. McKay

    (The Hong Kong University of Science and Technology
    University of Melbourne
    The Peter Doherty Institute for Infection and Immunity, University of Melbourne
    The Hong Kong University of Science and Technology)

  • Leo L. M. Poon

    (The University of Hong Kong
    Hong Kong Science and Technology Park
    The University of Hong Kong)

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.

Suggested Citation

  • 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 & Leo L. M. Poon, 2023. "Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37468-y
    DOI: 10.1038/s41467-023-37468-y
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    Cited by:

    1. Vivak Soni & John W. Terbot & Jeffrey D. Jensen, 2024. "Population genetic considerations regarding the interpretation of within-patient SARS-CoV-2 polymorphism data," Nature Communications, Nature, vol. 15(1), pages 1-5, December.
    2. Ruopeng Xie & Kimberly M. Edwards & Dillon C. Adam & Kathy S. M. Leung & Tim K. Tsang & Shreya Gurung & Weijia Xiong & Xiaoman Wei & Daisy Y. M. Ng & Gigi Y. Z. Liu & Pavithra Krishnan & Lydia D. J. C, 2023. "Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Mark P. Khurana & Jacob Curran-Sebastian & Neil Scheidwasser & Christian Morgenstern & Morten Rasmussen & Jannik Fonager & Marc Stegger & Man-Hung Eric Tang & Jonas L. Juul & Leandro Andrés Escobar-He, 2024. "High-resolution epidemiological landscape from ~290,000 SARS-CoV-2 genomes from Denmark," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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