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

Abstract

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, the severity of liver damage has been shown to correlate with higher mortality. Overall, the mechanism behind the liver injury remains unclear. We showed in this study 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. Our findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

SciScore for 10.1101/2021.02.10.21251458: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	Consent: Liver biopsies were obtained during operations with full informed consent from parents or patients, and the study was approved by Hong Kong West Cluster-Hong Kong University Cluster Research Ethics Committee/Institutional Review Board (UW 16-052) IRB: Liver biopsies were obtained during operations with full informed consent from parents or patients, and the study was approved by Hong Kong West Cluster-Hong Kong University Cluster Research Ethics Committee/Institutional Review Board (UW 16-052)
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.
Cell Line Authentication	not detected.

Table 2: Resources

Experimental Models: Cell Lines
Sentences	Resources
The viral titers in the culture supernatants were measured at 1, 24, 48, and 72 h after infection using the TCID50 assay in Vero-E6 cells.	Vero-E6 suggested: None
Software and Algorithms
Sentences	Resources
Single cell transcriptomic data have been uploaded to NCBI Sequence Read Archive (SRA) and can be found with accession number: PRJNA609259.	Sequence Read Archive suggested: (DDBJ Sequence Read Archive, RRID:SCR_001370)
Photos were compiled using Adobe Photoshop CS6.	Adobe Photoshop suggested: (Adobe Photoshop, RRID:SCR_014199)
Statistical analysis: Statistical analysis was done using GraphPad Prism software version 9.	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798)

Results from OddPub: Thank you for sharing your data.

Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

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

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