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Published on: November 5, 2021
Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues
Meng-Yuan Li1,2, Lin Li1,2, Yue Zhang3,4,5
1Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
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.
Insights
Angiotensin-converting enzyme 2 (ACE2) is expressed in many human tissues, not just the lungs, suggesting SARS-CoV-2 can infect diverse organs. ACE2 expression is similar across sexes and ages, but correlates with immune responses, potentially explaining varied COVID-19 severity.
Area of Science:
- Virology and Immunology
- Human Physiology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic.
- The virus utilizes angiotensin-converting enzyme 2 (ACE2) as its primary cell entry receptor.
- Understanding ACE2 expression is crucial for elucidating SARS-CoV-2 infection mechanisms.
Purpose of the Study:
- To investigate ACE2 expression patterns across various normal human tissues.
- To compare ACE2 expression between different demographic groups (sex, age).
- To explore the relationship between ACE2 expression and immune signatures in human tissues.
Main Methods:
- Compared ACE2 expression levels in 31 normal human tissues.
- Utilized two-sided Student's t-test for demographic comparisons (sex, age).
- Employed Pearson's correlation test to assess ACE2 expression and immune signature correlations.
Main Results:
- Highest ACE2 expression observed in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue.
- Lowest ACE2 expression found in blood, spleen, bone marrow, brain, blood vessels, and muscle.
- ACE2 expression did not differ significantly between sexes or age groups; however, correlations with immune signatures varied by tissue, sex, and age.
Conclusions:
- SARS-CoV-2 can potentially infect tissues beyond the lungs.
- ACE2 expression is consistent across diverse sexes and ages, indicating equal susceptibility.
- Differential host immune responses, influenced by ACE2 expression correlations, may contribute to varied COVID-19 disease severity.
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