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SARS-CoV-2 Omicron efficiently infects human airway, but not alveolar epithelium
Mart M Lamers; Anna Z Mykytyn; Tim I Breugem; Nathalie Groen; Kevin Knoops; Debby Schipper; Romy van Acker; Petra B van den Doel; Theo Bestebroer; Charlotte D Koopman; Chantal Reusken; Mauro J Muraro; Corine H GeurtsvanKessel; Martin E van Royen; Peter J Peters; Jingshu Zhang; Bart L Haagmans.
Affiliation
  • Mart M Lamers; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Anna Z Mykytyn; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Tim I Breugem; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Nathalie Groen; Single Cell Discoveries, Utrecht, The Netherlands.
  • Kevin Knoops; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, Netherlands.
  • Debby Schipper; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Romy van Acker; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Petra B van den Doel; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Theo Bestebroer; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Charlotte D Koopman; Single Cell Discoveries, Utrecht, The Netherlands.
  • Chantal Reusken; Centre for Infectious Disease Control, WHO COVID-19 Reference Laboratory, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
  • Mauro J Muraro; Single Cell Discoveries, Utrecht, The Netherlands.
  • Corine H GeurtsvanKessel; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Martin E van Royen; Department of Pathology Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Peter J Peters; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, Netherlands.
  • Jingshu Zhang; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Bart L Haagmans; Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands.
Preprint in English | bioRxiv | ID: ppbiorxiv-476898
ABSTRACT
In late 2021, the highly mutated SARS-CoV-2 Omicron variant emerged, raising concerns about its potential extensive immune evasion, increased transmissibility and pathogenicity. Here, we used organoids of the human airways and alveoli to investigate Omicrons fitness and replicative potential in comparison with earlier SARS-CoV-2 variants. We report that Omicron replicates more rapidly in the airways and has an increased fitness compared to the early 614G variant and Delta. In contrast, Omicron did not replicate productively in human alveolar type 2 cells. Mechanistically, we show that Omicron does not efficiently use TMPRSS2 for entry or spread through cell-cell fusion. Altogether, our data show that Omicron has an altered tropism and protease usage, potentially explaining its higher transmissibility and decreased pathogenicity.
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2022 Document type: Preprint
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