PT  - JOURNAL ARTICLE
AU  - Miguel Ortiz Bezara
AU  - Andrew Thurman
AU  - Alejandro Pezzulo
AU  - Mariah R. Leidinger
AU  - Julia A. Klesney-Tait
AU  - Philip H. Karp
AU  - Ping Tan
AU  - Christine Wohlford-Lenane
AU  - Paul B. McCray, Jr.
AU  - David K. Meyerholz
TI  - Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract
AID  - 10.1101/2020.04.22.056127
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.22.056127
4099  - http://biorxiv.org/content/early/2020/04/23/2020.04.22.056127.short
4100  - http://biorxiv.org/content/early/2020/04/23/2020.04.22.056127.full
AB  - Rationale Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current coronavirus disease 2019 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 cellular receptor for SARS-CoV-2. Receptor expression on the cell surface facilitates viral binding and entry. However, reports of the abundance and distribution of ACE2 expression in the respiratory tract are limited and conflicting.Objectives To determine ACE2 expression in the human respiratory tract and its association with demographic and clinical characteristics.Methods Here, we systematically examined human upper and lower respiratory tract cells using single-cell RNA sequencing and immunohistochemistry to determine where the receptor is expressed.Measurements and main results Our results reveal that ACE2 expression is highest within the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma where severe disease occurs, ACE2 was found on the apical surface of a small subset of alveolar type II cells. We saw no increase of receptor expression in the presence of known risk factors for severe coronavirus disease 2019.Conclusions The mapping of ACE2 to specific anatomical regions and to particular cell types in the respiratory tract will help guide future studies and provide molecular targets for antiviral therapies.Competing Interest StatementThe authors have declared no competing interest.