Higher Expression of ACE-2 in Smokers and COPD Patients May Increase Risk of Severe COVID-19 Infection

Significance 

With COVID-19 cases soaring, health care officials are trying to get ahead of the worst by looking at who is most at risk of ending up in the ICU and on ventilators if they catch the virus. High on that list is smokers. There are already so many reasons not to smoke: increased risk of heart disease, stroke and cancer. Indeed recent study by University of British Columbia scientists suggest that giving up smoking could lessen the chance that an infection with SARS-CoV-2 coronavirus will lead to severe COVID-19 disease. Their studies found that the lung cells of people who are current cigarette smokers, and individuals with chronic obstructive pulmonary disease (COPD), have increased levels of the angiotensin converting enzyme II (ACE-2) receptor that the SARS-CoV-2 virus uses to gain entry into host cells and cause infection.

The research was led by Dr. Janice Leung, who is a clinical assistant professor at the University of British Columbia and St. Paul’s Hospital in Canada. They also found that former smokers had similar levels of ACE-2 to people who had never smoked. This suggests that there has never been a better time to quit smoking to protect a person from COVID-19 infection. Moreover, the study suggests patients with COPD should be counseled to strictly abide by social distancing and proper hand hygiene to prevent infection. The research work is now published in European Respiratory Journal.

SARS-CoV-2 uses the ACE-2 receptor as a cellular entry receptor and while the virus can infect people of any age, most of the severe cases, to date, have been in individuals over the age of 55 years and with significant comorbidities and underlying chronic diseases such as lung and cardiovascular diseases.

“We hypothesized that this could be because the levels of ACE-2 in their airways might be increased compared to people without COPD, which could possibly make it easier for the virus to infect the airway,” Leung suggested. To look into this possibility the researchers analyzed lower respiratory tract bronchial epithelial cells obtained from the lungs of 21 COPD patients and 21 individuals without COPD, to determine ACE-2 expression. They looked at their resulting data in the context of factors, such as whether the samples were from people who had either never smoked, were current smokers, or former smokers.

The results confirmed higher ACE-2 expression levels in the samples from the COPD patients, and also in the samples from people who were current smokers. “ACE-2 expression in the epithelial cells was significantly increased in COPD versus non-COPD subjects,” the team noted. “Interestingly, smoking status was also significantly related to ACE-2 gene expression levels in airways of these participants with current smokers having a significantly higher gene expression than never smokers.”

The researchers then validated their findings against two existing study groups, which together contain data on a further 249 people—some non-smokers, some current smokers, and some former smokers. Again, they found that levels of ACE-2 were higher in current smokers, but lower in non-smokers and former smokers. They noted that their study did have some limitations, but pointed out that the results are consistent with observations from previous studies in small animals, which found that smoke exposure upregulated both the expression and activity of ACE-2 in the airways.

The research team noted that their findings indicate that active cigarette smoking and COPD upregulate ACE-2 expression in the lower airways, which may in part explain the increased risk of severe COVID-19 in these patients. Although it is well established that upregulation of ACE-2 may protect patients against acute lung injury, chronically, this may predispose individuals to increased risk of coronavirus infections, which uses this receptor to gain entrance into epithelial cells.

They concluded, “These findings highlight the importance of smoking cessation for these individuals and increased surveillance of these risk subgroups for prevention and rapid diagnosis of this potentially deadly disease.”

In a nutshell, the UBC study exciting mechanistic insight into why some people may be at risk of more severe COVID-19 symptoms than others. It will be interesting in future studies whether changing ACE-2 expression levels improve survival in patients infected with COVID-19.

Higher Expression of ACE2 in Smokers and COPD Patients May Increase Risk of Severe COVID-19 Infection - Medicine Innovates

About the author

Janice M. Leung, MD

Dr. Janice Leung completed her Bachelor’s Honours degree in History and Science at Harvard University and Doctor of Medicine degree at Johns Hopkins University. Dr. Leung is an American Board certified Pulmonary Medicine, Internal Medicine, and Critical Care Medicine specialist, and a Canadian Royal College certified fellow in Respirology and Internal Medicine. In 2015, she completed her Postdoctoral Fellowship with Dr. Don Sin at the Centre for Heart Lung Innovation and was appointed Clinical Assistant Professor in the Division of Respiratory Medicine within the UBC Department of Medicine.

Dr. Leung is a recipient of the Michael Smith Foundation for Health Research Health Professional Investigator Award, CIHR-AstraZeneca Early Career Investigator Award, and operating grants from CIHR, BC Lung Association, and Genome BC. Dr. Leung’s commitment to teaching has been recognized by a number of distinctions, including the Faculty of Medicine Clinical Faculty Award for Excellence in Clinical Teaching (2018), the St. Paul’s Hospital Graeme Copland Clinical Teacher Award (2017), and the Fay R. Dirks Award for Excellence in Teaching at UBC (2017).

Dr. Leung is studying the clinical outcomes, manifestations, and underlying mechanisms of HIV-associated chronic obstructive pulmonary disease. In particular, she is interested in the pathogenesis of accelerated aging in the lung and has detected signs of accelerated aging using the blood and airway epithelial cells from HIV-infected patients. Platforms for this research include next generation sequencing methylomics and transcriptomics as well as the microbiome.

Reference

Janice M. Leung, Chen X. Yang, Anthony Tam, Tawimas Shaipanich, Tillie-Louise Hackett, Gurpreet K. Singhera, Delbert R. Dorscheid, Don D. Sin. ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19. European Respiratory Journal 2020; DOI: 10.1183/13993003.00688-2020

Go To European Respiratory Journal

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