Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication and its comparison with SARS-CoV

  1. Vincent Chi-Hang Lui
  2. Kenrie Pui-Yan Hui
  3. Rosanna Ottakandathil Babu
  4. Haibing Yue
  5. Patrick Ho-Yu Chung
  6. Paul Kwong-Hang Tam
  7. Michael Chi-Wai Chan
  8. Kenneth Kak-Yuen Wong
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Abstract

Background

Although the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, patients with severe liver disease have been shown to have higher mortality. Overall, the mechanism behind the liver injury remains unclear.

Approach and results

We showed that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV.

Conclusion

Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

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