SARS-CoV-2, a novel coronavirus that causes the COVID-19 disease, uses a receptor called angiotensin-converting enzyme 2 (ACE2) to gain entry into human cells. A new study published in the European Heart Journal, shows that men have higher concentrations of ACE2 in their blood plasma than women; this could explain why men might be more susceptible to infection with, or the consequences of, SARS-CoV-2.
“ACE2 is a receptor on the surface of cells,” said Professor Adriaan Voors, a researcher in the University Medical Center Groningen and corresponding author of the study.
“It binds to the coronavirus and allows it to enter and infect healthy cells after it has been modified by another protein on the surface of the cell, called TMPRSS2.”
“High levels of ACE2 are present in the lungs and, therefore, it is thought to play a crucial role in the progression of lung disorders related to COVID-19.”
Professor Voors and colleagues were already studying differences in markers of disease in the blood between men and women before the coronavirus outbreak.
“When we found that one of the strongest biomarkers, ACE2, was much higher in men than in women, I realized that this had the potential to explain why men were more likely to die from COVID-19 than women,” said first author Dr. Iziah Sama, also from the University Medical Center Groningen.
The team measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 European countries.
The study involved 1,485 men and 537 women with heart failure (index cohort); the results were validated in 1,123 men and 575 women (validation cohort).
When the researchers looked at a number of clinical factors that could play a role in ACE2 concentrations, including the use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), as well as a history of chronic obstructive pulmonary disease, coronary artery by-pass graft and atrial fibrillation, they found that male sex was the strongest predictor of elevated ACE2 concentrations.
In the index cohort, ACEIs, ARBs and MRAs were not associated with greater ACE2 plasma concentrations, and in the validation cohort, ACEIs and ARBs were associated with lower ACE2 concentrations, while MRAs were only weakly associated with higher concentrations.
“To the best of our knowledge, this is the first substantial study to examine the association between plasma ACE2 concentrations and the use of blockers of the renin-angiotensin-aldosterone system in patients with cardiovascular disease,” Professor Voors said.
“We found no evidence that ACEIs and ARBs were linked to increased ACE2 concentrations in plasma.”
“In fact, they predicted lower concentrations of ACE2 in the validation cohort, although we did not see this in the index cohort.”
“The effect of MRAs on ACE2 concentrations is not clear, as the weak increase in concentrations in the validation cohort was not seen in the index cohort.”
“Our findings do not suggest that MRAs should be discontinued in heart failure patients who develop COVID-19. They are a very effective treatment for heart failure and the hypothetical effects on viral infection should be weighed carefully against their proven benefits.”
Iziah E. Sama et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of rennin-angiotensin-aldosterone inhibitors. European Heart Journal, published online May 10, 2020; doi: 10.1093/eurheartj/ehaa373
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