Evidence from a large study of several thousand patients shows that men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in their blood than do women. Since ACE2 enables the coronavirus to infect healthy cells, this may help to explain why men are more vulnerable to COVID-19 than women. The study, published in the European Heart Journal, also found that heart-failure patients taking drugs targeting the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), did not have higher concentrations of ACE2 in their blood.
Adriaan Voors, MD-PhD, professor of cardiology at the University Medical Center Groningen, The Netherlands, who led the study, said, “Our findings do not support the discontinuation of these drugs in COVID-19 patients as has been suggested by earlier reports.”
Some recent research suggested that RAAS inhibitors might increase concentrations of ACE2 in plasma—the liquid part of blood—thereby increasing the risk of COVID-19 for cardiovascular patients taking these drugs. The current study indicates that this is not the case, although it looked only at ACE2 concentrations in plasma, not in tissues such as lung tissue.
Dr. Voors said, “ACE2 is a receptor on the surface of cells. It binds to the coronavirus and allows it to enter and infect healthy cells after it is 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.”
Dr. Voors and his colleagues were already studying differences in markers of disease in the blood between men and women before the coronavirus outbreak. The results became available soon after the pandemic began.
The researchers measured ACE2 concentrations in blood samples taken from two groups of heart-failure patients from 11 European countries. There were 1,485 men and 537 women in the first group, the index cohort, which was designed to test the researchers’ hypotheses and research questions. Then the researchers validated their findings in a second group of 1,123 men and 575 women, the validation cohort. The median age in the index cohort was 69 years for men and 75 years for women, and in the validation cohort it was 74 and 76 years, respectively.
When the researchers looked at several clinical factors that could play a role in ACE2 concentrations, including the use of ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists, as well as a history of COPD, coronary artery bypass graft, and atrial fibrillation, they found that male sex was the strongest predictor of elevated ACE2 concentrations.
For more about the impact of gender and other influencers on COVID-19 outcomes, see “COVID-19 News Digest,” page 44.