Data from The Cancer Genome Atlas (TCGA) database show how cancerous tissues and lung tissue from smokers are associated with increased ACE 2 expression and ACE 2 mRNA expression.  This supports the finding that cancer patients have a greater risk for developing COVID-19 and having a poor prognosis.  

Michigan State University

Increased, ectopic expression of human ACE2 in transgenic mice has been shown to correlate with an increase in SARS-CoV replication, coupled with an increase in expression of the genes furthering viral reproduction. It is hypothesized that ACE2 expression may aid viral entry and/or replication, and pose as a risk factor for COVID-19 infection/severity.

- ACE2 and viral entry: low ACE2 Expression as sufficient for SARS-CoV-2 Infection
- ACE2 and comorbidities: increased ACE2 expression in cancerous tissues


Increased ACE2 Expression as a Risk Factor for COVID-19

Tan, H. W., Xu, Y. M., & Lau, A. T. Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection. Reviews in Medical Virology, e2122. https://onlinelibrary.wiley.com/doi/full/10.1002/rmv.2122

Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection

Cancerous Tissues are Associated with Increased ACE 2 Expression

SARS-CoV-2 targets the respiratory system, yet ACE2 mRNA expression is low in the lungs. Viral entry in these low-expressing tissues may be caused by the structure of the virus's S protein. The furin cleaving site at the S1-S2 junction, where the S1 and S2 subunits of the S protein meet, is not present in other SARS viruses. Studies with SARS-CoV show that inserting a cleavage site at this location modestly but significantly increases membrane fusion, possibly aiding infection in low ACE2 expressing tissue.

Low ACE2 Expression sufficient for SARS-CoV-2 Infection

Several studies (immunohistochemistry and transcriptomic analysis) show that the following relationship exists between ACE2 expression and smokers:

smokers with chronic obstruction pulmonary disease (COPD) > healthy smokers > nonsmokers

Increased expression was noticed in alveolar type 2 progenitor cells (AT 2), alveolar macrophages, and the small airway epithelium.  This phenomenon is thought to play a role in the metabolic changes that lead to the replication of SARS-CoV-2.  Additionally, cigarette smoke is a common risk factor for many other respiratory diseases.  

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