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.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Gene expression; Immune signatures; SARS-CoV-2; SARS-CoV-2 cell receptor; SARS-CoV-2 pandemic.

Fig. 1

ACE2 expression in various human tissues. a Comparison of ACE2 expression levels across 31 human tissues in GTEx [10]. Comparison of ACE2 expression levels between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) groups in individual human tissues in GTEx (b) and TCGA (c). In TCGA, a comparison of ACE2 expression levels between Asian and non-Asian races in five normal human tissues was also performed (c). Two-sided Student’s t test was used in (b, c). The adjusted P value was calculated by the Benjamini and Hochberg method [13]. ACE2: Angiotensin-converting enzyme 2; GTEx: Genotype-Tissue Expression; TCGA: The Cancer Genome Atlas

Fig. 2

Association of ACE2 expression with immune signatures in various human tissues. a Correlation between ACE2 expression levels and immune signature enrichment levels in various human tissues in males and females. b Correlation between ACE2 expression levels and immune signature enrichment levels in the lungs and thyroid of older (ages > 49 years) and younger (ages ≤49 years) populations. Pearson’s correlation test was used to calculate the correlation coefficient (r) and P value in (a, b). * P < 0.05, ** P < 0.01, and *** P < 0.001. ACE2: Angiotensin-converting enzyme 2; NK: Natural killer