Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interaction...

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Bibliographic Details
Published in:bioRxiv 2020-08
Main Authors: Ortiz Bezara, Miguel E, Thurman, Andrew, Pezzulo, Alejandro A, Leidinger, Mariah R, Klesney-Tait, Julia A, Karp, Philip H, Tan, Ping, Wohlford-Lenane, Christine, Mccray, Paul B, Meyerholz, David K
Format: Article
Language:English
Subjects:
ACE2
Alveoli
Angiotensin-converting enzyme 2
Coronaviruses
COVID-19
Disease transmission
Immunohistochemistry
Localization
mRNA
Pandemics
Parenchyma
Proteins
Respiratory tract
Risk factors
Severe acute respiratory syndrome coronavirus 2
Zoonoses
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Summary:Background: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. Materials and methods: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. Findings: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. Interpretation: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.04.22.056127