Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
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Abstract
A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.
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SciScore for 10.1101/2020.02.03.931766: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical approval was obtained from the research ethics committee of Zhongshan Hospital, Fudan University, and written informed consent was obtained from each patient.
Consent: Ethical approval was obtained from the research ethics committee of Zhongshan Hospital, Fudan University, and written informed consent was obtained from each patient.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Public dataset acquisition and processing: Gene expression matrix and cell type annotation of scRNA-seq data of normal human liver were downloaded … SciScore for 10.1101/2020.02.03.931766: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical approval was obtained from the research ethics committee of Zhongshan Hospital, Fudan University, and written informed consent was obtained from each patient.
Consent: Ethical approval was obtained from the research ethics committee of Zhongshan Hospital, Fudan University, and written informed consent was obtained from each patient.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Public dataset acquisition and processing: Gene expression matrix and cell type annotation of scRNA-seq data of normal human liver were downloaded from the Gene Expression Omnibus (GEO124395). Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We could not exclude the possibility of technical limitations in detecting extremely low ACE2 expression in hepatocytes at this point. This study demonstrated the highly sensitive nature of single-cell resolution analysis and facilitated the understanding of the mechanisms of liver malfunction in 2019-nCoV-infected patients. Such information call for patient cares regarding liver responses, especially related to cholangiocyte function, of the large number of 2019-nCoV patients currently under emergency and potential post-cure treatment for liver recovery after hospitalization.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- No funding statement was detected.
- No protocol registration statement was detected.
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