key: cord-1002286-cfktjerw
authors: Pirola, Carlos J; Sookoian, Silvia
title: SARS‐CoV‐2 virus and liver expression of host receptors: Putative mechanisms of liver involvement in COVID‐19
date: 2020-04-30
journal: Liver Int
DOI: 10.1111/liv.14500
sha: 5e5bfa925539ec9fa3da8692b7e0336022dd7d55
doc_id: 1002286
cord_uid: cfktjerw

Zhang et al. showed that COVID‐19 affected patients’ present liver biochemistry abnormalities, including elevation of aminotransferases, gamma‐glutamyl transferase, and alkaline phosphatase (1). Hence, several possible clinical scenarios in the setting of liver diseases have been postulated. First, patients with chronic liver disease may be more vulnerable to the severe clinical consequences of COVID‐19, including oxygen desaturation and hypoxemia due to severe pneumonia or the cytokine storm (1;2). Second, liver biochemistry abnormalities are the consequence of drug toxicity.

To the Editor, Zhang et al. showed that COVID-19 affected patients' present liver biochemistry abnormalities, including elevation of aminotransferases, gamma-glutamyl transferase, and alkaline phosphatase 1 .

Hence, several possible clinical scenarios in the setting of liver diseases have been postulated.

First, patients with chronic liver disease may be more vulnerable to the severe clinical consequences of COVID-19, including oxygen desaturation and hypoxemia due to severe pneumonia or the cytokine storm 1;2 . Second, liver biochemistry abnormalities are the consequence of drug toxicity.

There is a third potential but poorly explored clinical scenario, which is the possibility that the novel 2019 coronavirus, also known as SARS-CoV-2, may directly or indirectly cause liver injury.

In fact, SARS-CoV2 viral load in the stool, which has been detected in about 48% of patients even in stool collected after respiratory samples tested negative 3 , is likely to be associated with portal venous viremia.

We assessed the gene expression levels of SARS-CoV2-interacting host receptors in the liver tissue and their distribution across cell types according to single-cell transcriptomic experiments retrieved from the Single Cell Portal. We focused on angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and paired basic amino acid cleaving enzyme (FURIN) gene expression levels. Our analysis shows that the three human host receptors are expressed in the liver tissue; however, expression levels extensively vary across cell types. ACE2

presents the highest expression levels in cholangiocytes, followed by hepatocytes ( Figure 1C) .

TMPRSS2 is expressed in cholangiocytes, hepatocytes, periportal liver sinusoidal endothelial cells, erytroid cells, and in a much lesser extent in non-inflammatory macrophages and alpha-beta T cells ( Figure 1D) . FURIN shows expression levels across all cell types, from hepatocytes to all populations of liver resident cells ( Figure 1E) .

Together, these findings support the possibility that SARS-CoV-2 may cause direct liver injury by viral cytopathic effect (directly by lysis and/or by inducing necrotic/apoptotic effect/s). showed not only liver impairment in up to 60% of the patients but also confirmed the presence of

This article is protected by copyright. All rights reserved SARS-coronavirus by RT-PCR in liver biopsies presenting mild to moderate lobular inflammation and apoptosis 4 .

In conclusion, to understand the pathogenesis of SARS-CoV-2 -related liver disease, additional research must be guaranteed, including the search for evidence of viral replication in hepatocytes and liver histology characterization.

Author contributions: SS: study concept and design; data acquisition; data analysis and interpretation; manuscript drafting; securing funding. CJP: study concept and design; data acquisition; data analysis and interpretation; manuscript drafting; securing funding.

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