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

Abstract

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.

Sex-dependent immune response and lethality of COVID-19

“…It is rare for the infected kids to be hospitalized and less than 1% of pediatric cases may become fatal ( Pierce et al, 2020 , Snape and Viner, 2020 , Swann et al, 2020 ). It may not be because of the reduced ACE2 levels in the respiratory tract of the kids as one might have suspected ( Ortiz et al, 2020 ). Nevertheless, more and more children have been infected with SARS-CoV-2 worldwide as the pandemic continues.…”

COVID-19 Pneumonia in Children: From Etiology to Management

“…However, studies do not unilaterally support this hypothesis. In fact, some evidence suggests that ACE2 expression in children is neither up- nor downregulated ( 35 , 36 ). On the other hand, another study found that ACE2 is downregulated once the virus penetrates the cell and replicates, resulting in fewer receptors upon which the virus can act ( 37 ).…”

SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature

“…Several reports indicate a wide, although variable, distribution of ACE2 expression patterns among different tissues (7)(8)(9), thus underlining a potential different virus infection susceptibility among cell types. The fact that COVID-19 disease may lead to multiple organ failure (10,11) shows the crucial relevance for understanding the molecular mechanisms of host cell factors used by SARS-CoV-2 to infect their target tissues.…”