SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo
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,
Malik Peiris,
John M. Nicholls and
Michael C. W. Chan ()
Additional contact information
Kenrie P. Y. Hui: The University of Hong Kong
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
Malik Peiris: The University of Hong Kong
John M. Nicholls: The University of Hong Kong
Michael C. W. Chan: The University of Hong Kong
Nature, 2022, vol. 603, issue 7902, 715-720
Abstract:
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.
Date: 2022
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DOI: 10.1038/s41586-022-04479-6
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