Men More Likely to Die From COVID-19 Than Women Because of Key Enzyme

The higher presence of angiotensin-converting enzyme 2 (ACE2) found in the heart, kidneys, in tissues lining blood vessels, and in particularly high levels in the testes, could explain why more men die from COVID-19, DailyMail reported.

ACE2 is a receptor on the surface of cells which binds to the new coronavirus and allows it to enter and infect cells.

While men and women are equally likely to catch the coronavirus, men are more likely to suffer severe effects of the disease, in part due to their higher levels of ACE2, according to the lead researcher.

'ACE2 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,' said Dr Adriaan Voors at the University Medical Center Groningen in The Netherlands.

'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.'

The study, published in the European Heart Journal, also found that widely-prescribed drugs called ACE inhibitors or angiotensin receptor blockers (ARBs) did not lead to higher ACE2 concentrations and should therefore not increase the COVID-19 risk for people taking them.

ACE inhibitors and ARBs – which are widely prescribed to patients with congestive heart failure, diabetes or kidney disease – account for billions of dollars in prescription sales worldwide.

'Our findings do not support the discontinuation of these drugs in COVID-19 patients,' said Dr Voors.

COVID-19, the respiratory disease caused by the novel coronavirus, has infected more than 4 million people worldwide and killed almost 277,000.

Death and infection rates suggest men are more likely than women to contract COVID-19 and suffer severe or critical complications as a result.

According to Chinese research, 58.1 per cent of men test positive for the illness compared with 41.9 per cent of women.

While an NHS England analysis of 17.4 million patient records discovered that men are 1.99 times as likely to die as women from the disease.

To find out more, Voors and his team measured ACE2 concentrations in blood samples from more than 3,500 heart failure patients from 11 European countries.

The study had started before the coronavirus pandemic, the researchers said, and so did not include patients with COVID-19.

But when other research began to point to ACE2 as key to the way the new coronavirus gets into cells, Voors and his team saw important overlaps with their study.

looking at clinical factors, including the use of ACE inhibitors, ARBs and chronic disease, they found male sex was the strongest predictor of elevated ACE2 concentrations.

The fact ACE2 was present in the testes might partially explain higher ACE2 concentrations in men, and why men are more vulnerable to COVID-19.

Because the sample of patients was so large, the results can likely be generalised to the real world setting, according to Professor Ian Hall, director of the Nottingham Biomedical Research Centre at the University of Nottingham, who wasn't involved in the research.

But there are likely to be other factors at play that are responsible for higher infection and death rates in men, he said.

'The actual difference in ACE2 levels between men and women, whilst statistically significant, is in real terms small, and I believe it likely that whilst this might contribute in a small way there must be other explanations as to why men are at increased risk of severe disease,' he said.

'One potential explanation would be that differential immune responses to the virus, regulated by genetic differences between men and women, may also underlie this difference in susceptibility.'

The research did have a few limitations – ACE2 was measured in blood samples and not in tissues such as lung tissue.

Patients looked at also had pre-existing heart failure and so may not be entirely representative of the general population, and perhaps most crucially, did not have COVID-19.