Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

By Xiaoqiang Chai, Longfei Hu, Yan Zhang, Weiyu Han, Zhou Lu, A. Ke, Jian Zhou, G. Shi, N. Fang, Jia Fan and 3 more. bioRxiv, 2020

978 citations recorded by the source corpus.

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.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/7c35647525120c76666ce6b75c34994db2771dbe

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Citations in the corpus

Biomarkers associated with COVID-19 disease progression (2020, background): “A recent study suggested that SARS-CoV-2 may directly bind to ACE2-positive cholangiocytes, and therefore, liver abnormalities in COVID-19 patients may be due to cholangiocyte dysfunction and other causes, such as druginduced and systemic inflammatory response-induced liver injuries [63].”
Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses (2020, background): “Since the outbreak, many data analysis have showed a wide distribution of ACE2 across human tissues, including lung[5], liver[6], stomach[7], ileum[7], colon[7] and kidney[8], indicating”
COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission (2020, neutral): “10 Altogether, substantial effort should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation, and early intervention.”
Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19 (2020, background): “hepatocytes, Kupffer cells, and the endothelial lining of the sinusoids were negative for ACE2; only cholangiocytes were positive for ACE2 [22, 23, 73].”
COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection (2021, background): “ACE2 expression is detected in type II alveolar cells (AT2) [22–26], bronchial transient epithelial secretory cells respiratory epithelial cells [27], myocardial cells [22], endothelial cells and artery smooth muscle cells [22], oesophagus epithelial cells [22–24], neurons and glia [28], tongue epit”
Clinical Features of COVID-19-Related Liver Functional Abnormality (2020, neutral): “9 Importantly, recent studies confirmed that ACE2 receptor is the cell entry receptor of SARS-CoV-2..”
COVID-19: Abnormal liver function tests (2020, background): “A new study found that the SARS-CoV-2 virus may bind to angiotensin-converting enzyme 2 (ACE2) on cholangiocytes, leading to cholangiocyte dysfunction and inducing a systemic inflammatory response leading to liver injury.(7) As of March 10, 2020, 7 relatively large-scale hospitalbased studies have r”
The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China (2020, neutral): “not necessarily hepatocytes via specific expression of ACE2 in healthy liver tissues using cell RNA-seq data of two independent cohorts [126].”
Coronavirus disease 2019 (COVID-19): current status and future perspectives (2020, background): “Besides pulmonary tissue, ACE2 is also highly expressed in other tissues, including bile duct, liver, gastrointestinal organs (small intestine, duodenum), esophagus, testis, and kidney [42, 117-119].”
Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies (2020, background): “Recent studies have shown that the novel coronavirus SARS-COV-2 binds to ACE2 receptors on target cells through the RBD on viral particles, leading to replication [7].”