Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

Abstract

Background: Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. Methods: We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test. Results: ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. Conclusions: Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

COVID-19, MERS and SARS with Concomitant Liver Injury—Systematic Review of the Existing Literature

“…Recently, Meng-Yuan et al compared ACE2 expression levels across 31 human tissues using the datasets from the Genotype-Tissue Expression (GTEx) project and the Cancer Genome Atlas (TCGA) program. The researchers were able to report highest ACE2 expression in the small intestine, testis, kidneys, heart, thyroid and adipose tissue and medium expression in the lungs, colon, liver, bladder and adrenal gland [57]. The study by Paizis et al [58] using immunohistochemistry confirmed ACE2 expression in hepatocytes of healthy human liver which increased in chronic liver diseases and during hypoxia.…”

Oral epithelial expression of angiotensin converting enzyme-2: Implications for COVID-19 diagnosis and prognosis

“…Membrane bound ACE2 is the port of entry for SARS-CoVs to the target cells. ACE2 transcript and protein expression has been reported in several human tissues by reverse transcriptase polymerase chain reaction and immunohistochemistry respectively 5,14,16 . We observed strong ACE2 expression in the epithelial cells of the oral mucosa.…”

“…Structurally, ACE2 is a type I transmembrane protein with a short C-terminal cytoplasmic tail, a hydrophobic transmembrane region, and a glycosylated amino terminal ectodomain containing the active site 4,5 . A soluble form of ACE2 (sACE2) has been shown to be released either constitutively or induced by inflammation.…”

“…The spike protein that protrudes from the surface of the virus is a type I glycoprotein that binds specific host cell receptor via a receptor binding domain facilitating viral entry into target cells 3 . The SARS-CoV-1 has been shown to use a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) as a receptor for target cell entry 4,5 . Positive correlation between ACE2 expression and SARS-CoV-1 infection has been observed 6 .…”

“…ACE2 is mainly expressed by epithelial cells of the lung, intestine, kidney, and colon (3). This may explain the high incidence of pneumonia and bronchitis in those with severe COVID-19 infection 5,14 . Analyses of the publicly available RNA data sets and immunohistochemical studies suggest that the ACE2 is also highly expressed in the skin and mucous membranes including the oral mucosa [15][16][17] .…”