- ACE2 may help explain why men are more vulnerable to infection with COVID-19
- The enzyme is found in the heart, kidneys and other organs including the testes
- But widely-prescribed drugs called ARBs don’t increase ACE2 levels, study finds
By Jonathan Chadwick For Mailonline , Published: 11 May 2020
Men’s blood has higher levels than women’s of a key enzyme used by the new coronavirus to infect cells, according to a new European study.
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.
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. 
Men are twice as likely to die from coronavirus as women, the biggest-ever study into the disease’s risk factors found
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.
After 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.
ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream, scientists say
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.
ACE2 ENABLES CORONAVIRUS TO INFECT HEALTHY HUMAN CELLS
ACE-2 receptors are structures found on the surface of cells in the lungs and airways which work with an enyzme called ACE (angiotensin-converting enzyme) to regulate blood pressure.
Its exact function in the lungs is not well understood but studies suggest it is protective against lung damage and low levels of it can worsen the impact of viral infections.
Scientists say that the coronavirus enters the body through the ACE-2 receptor, which the shape of it allows it to latch on to.
This means that someone with more ACE-2 receptors may be more susceptible to a large viral load – first infectious dose of a virus – entering their bloodstream.
ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream, scientists say +7
ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream, scientists say
People who have higher than usual numbers of ACE-2 receptors may include those with diabetes or high blood pressure because they have genetic defects which make them produce more. Emerging evidence shows that smokers may also produce more.
High levels of ACE-2 receptors may also be protective, however.
They are thought to be able to protect the lungs during infection and a study on mice in 2008 found that mice which had ACE-2 blocked in their bodies suffered more damage when they were infected with SARS, which is almost identical to COVID-19.
Smoking has in the past been repeatedly linked to lower than normal levels of ACE-2 receptors, potentially increasing the risk of lung damage from COVID-19.
