Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology

  1. Arthur Wickenhagen
  2. Meaghan Flagg
  3. Julia R. Port
  4. Claude Kwe Yinda
  5. Kerry Goldin
  6. Shane Gallogly
  7. Jonathan E. Schulz
  8. Tessa Lutterman
  9. Brandi N. Williamson
  10. Franziska Kaiser
  11. Reshma K. Mukesh
  12. Sarah van Tol
  13. Brian Smith
  14. Neeltje van Doremalen
  15. Colin A. Russell
  16. Emmie de Wit
  17. Vincent J. Munster

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Abstract

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.

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  1. Version published to 10.1038/s41467-025-55938-3
  2. Rapid Reviews Infectious Diseases

    Nishant Ranjan Chauhan

    Review 3: "Evolution of Omicron Lineage Towards Increased Fitness in the Upper Respiratory Tract in the Absence of Severe Lung Pathology"

    Reviewers found that the preprint was well-written and well-designed, but suggested several improvements in discussion section along with a number of minor comments.

  3. Rapid Reviews Infectious Diseases

    Yuan Shuofeng

    Review 2: "Evolution of Omicron Lineage Towards Increased Fitness in the Upper Respiratory Tract in the Absence of Severe Lung Pathology"

    Reviewers found that the preprint was well-written and well-designed, but suggested several improvements in discussion section along with a number of minor comments.

  5. Version published to 10.1101/2024.06.13.598902v1 on bioRxiv