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SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo

Author

Listed:
  • Kenrie P. Y. Hui

    (The University of Hong Kong
    Centre for Immunology and Infection (C2I), Hong Kong Science Park)

  • John C. W. Ho

    (The University of Hong Kong)

  • Man-chun Cheung

    (The University of Hong Kong)

  • Ka-chun Ng

    (The University of Hong Kong)

  • Rachel H. H. Ching

    (The University of Hong Kong)

  • Ka-ling Lai

    (The University of Hong Kong)

  • Tonia Tong Kam

    (The University of Hong Kong)

  • Haogao Gu

    (The University of Hong Kong)

  • Ko-Yung Sit

    (Queen Mary Hospital)

  • Michael K. Y. Hsin

    (Queen Mary Hospital)

  • Timmy W. K. Au

    (Queen Mary Hospital)

  • Leo L. M. Poon

    (The University of Hong Kong
    Centre for Immunology and Infection (C2I), Hong Kong Science Park)

  • Malik Peiris

    (The University of Hong Kong
    Centre for Immunology and Infection (C2I), Hong Kong Science Park)

  • John M. Nicholls

    (The University of Hong Kong)

  • Michael C. W. Chan

    (The University of Hong Kong
    Centre for Immunology and Infection (C2I), Hong Kong Science Park)

Abstract

The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines1, but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations.

Suggested Citation

  • Kenrie P. Y. Hui & John C. W. Ho & Man-chun Cheung & Ka-chun Ng & Rachel H. H. Ching & Ka-ling Lai & Tonia Tong Kam & Haogao Gu & Ko-Yung Sit & Michael K. Y. Hsin & Timmy W. K. Au & Leo L. M. Poon & M, 2022. "SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo," Nature, Nature, vol. 603(7902), pages 715-720, March.
    • Handle: RePEc:nat:nature:v:603:y:2022:i:7902:d:10.1038_s41586-022-04479-6
    DOI: 10.1038/s41586-022-04479-6
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    Cited by:

    1. Sabrina Semeraro & Anastasia Serena Gaetano & Luisa Zupin & Carlo Poloni & Elvio Merlach & Enrico Greco & Sabina Licen & Francesco Fontana & Silvana Leo & Alessandro Miani & Francesco Broccolo & Pierl, 2022. "Operative Protocol for Testing the Efficacy of Nasal Filters in Preventing Airborne Transmission of SARS-CoV-2," IJERPH, MDPI, vol. 19(21), pages 1-12, October.
    2. Han, Lili & Song, Sha & Pan, Qiuhui & He, Mingfeng, 2023. "The impact of multiple population-wide testing and social distancing on the transmission of an infectious disease," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 630(C).
    3. Catherine Park & Shahriar Tavakoli-Tabasi & Amir Sharafkhaneh & Benjamin J. Seligman & Bret Hicken & Christopher I. Amos & Andrew Chou & Javad Razjouyan, 2023. "Inflammatory Biomarkers Differ among Hospitalized Veterans Infected with Alpha, Delta, and Omicron SARS-CoV-2 Variants," IJERPH, MDPI, vol. 20(4), pages 1-11, February.
    4. Feng, Jingxue & Wang, Liangliang, 2024. "A switching state-space transmission model for tracking epidemics and assessing interventions," Computational Statistics & Data Analysis, Elsevier, vol. 197(C).

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