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

TLDR

The novel coronavirus 2019‑nCoV, first identified in December 2019, uses the ACE2 receptor to infect cells, and many patients exhibit liver damage whose mechanism remains unclear. The study aimed to determine which liver cell types express ACE2. Using single‑cell RNA‑seq from two independent cohorts, the authors mapped ACE2 expression and found it localized to cholangiocytes. The study found that 2019‑nCoV can bind to ACE2‑positive cholangiocytes, implying liver injury arises from cholangiocyte dysfunction rather than hepatocyte damage, and recommends vigilant liver monitoring during and after treatment.

Abstract

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.