Researchers find why men are more prone to Covid-19 than women

A study involving thousands of patients from Europe shows that men have higher concentrations of angiotensin-converting enzyme 2 (ACE2), an enzyme that enables the SARS-CoV-2 virus infect healthy cells in their blood, than women and this may probably help explain why men are more vulnerable to Covid-19 than women.

The study, published in the European Heart Journal on Monday, 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.

The study

“Our findings do not support the discontinuation of these drugs in Covid-19 patients as has been suggested by earlier reports,” said Dr Adriaan Voors, Professor of Cardiology at the University Medical Center Groningen in the Netherlands, who led the study, in a statement.

Some recent research suggested that RAAS inhibitors might increase concentrations of ACE2 in plasma, i.e., 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.

“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,” said Voors.

When we found that one of the strongest biomarkers, ACE2, was much higher in men than in women, I realised that this had the potential to explain why men were more likely to die from Covid-19 than women,” said Iziah Sama, Dr Voor’s colleague and first author of the study.

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.

Major limitation

ACE2 is found not only in the lungs, but also the heart, kidneys and the tissues lining blood vessels, and there are particularly high levels in the testes.

The researchers speculate that its regulation in the testes might partially explain higher ACE2 concentrations in men, and why men are more vulnerable to Covid-19.

One major limitation of the study is that the researchers only measured concentrations of ACE2 in plasma, not in tissues, so they cannot be sure that concentrations in the blood are similar to those seen in tissues; it is the ACE2 in the lung tissues that are thought to be important for viral infection of the lungs, not ACE2 concentrations in the blood.