Discovery may suggest why there is a higher rate of Covid-19 among men

A study of several thousand people has shown men have higher concentrations of an enzyme that enables the coronavirus to infect healthy cells.

While there is still much to learn about Covid-19, researchers from the University Medical Center Groningen in the Netherlands may have found a clue for solving one of its mysteries.

Writing in the European Heart Journal, the researchers said they have found in a study of several thousand patients that men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in their blood than women. ACE2 enables the coronavirus to infect healthy cells.

First author of the study, Dr Iziah Sama, said that this had the potential to explain why men were more likely to die from Covid-19 than women. The research measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 European countries.

ACE2 is found not only in the lungs, heart, kidneys and tissues lining blood vessels, but in high concentration in the testes. The researchers speculated that its regulation in the testes might partially explain higher ACE2 concentrations in men, and why men are more vulnerable to Covid-19.

There were 1,485 men and 537 women in the first index group, with a second group designed to validate the first groups’ findings, made up of 1,123 men and 575 women. The median age of those taking part was 69 years for men and 75 years for women. In the validation group, it was 74 years and 76 years, respectively. All patients had heart failure and did not have Covid-19.

What the study looked for

The study looked at a number of clinical factors that could contribute to ACE2 concentrations. These included using ACE inhibitors and mineralocorticoid receptor antagonists (MRAs), or whether there was any history of medical conditions such as chronic obstructive pulmonary disease or having had a coronary artery bypass graft.

“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 (RAAS) in patients with cardiovascular disease,” said Dr Adriaan Voors, who led the study.

“We found no evidence that ACE inhibitors and [angiotensin receptor blockers] 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.”

Recent research suggested that RAAS inhibitors might increase ACE2 concentrations in plasma, thereby increasing the risk of Covid-19 in cardiovascular patients. However, Voors said these latest findings don’t support the idea of discontinuing RAAS drug use in these patients.

“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.”