Men are more vulnerable to COVID-19 than women - and international researchers believe they may have found out why.
A study of thousands of patients across 11 European countries found men have higher concentrations of an enzyme, angiotensin-converting enzyme (ACE2), in their blood than women. Research has shown this enzyme helps SARS-CoV-2, the strain of coronavirus responsible for causing COVID-19, infect healthy cells.
The study, conducted by University of Groningen researchers in the Netherlands, has found new evidence to suggest why men with heart failure suffer more from COVID-19 than women.
The study, published in the European Heart Journal on Monday, found that heart failure patients taking drugs targeting the renin-angiotensin-aldosterone system (RAAS) - a hormone system responsible for regulating blood pressure, fluid and electrolyte balance - didn't have greater concentrations of the enzyme in their blood.
Some recent research suggests that drugs, such as RAAS inhibitors, may increase concentrations of the enzyme in plasma, therefore increasing the risk of COVID-19 for cardiovascular patients taking these drugs. However, the new study suggests this isn't the case.
Dr Adriaan Voors, a cardiology professor who led the study, says the enzyme binds to the coronavirus and allows it to enter and infect healthy cells, after it has been modified by another protein on the cell surface, 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," Voors said in a statement.
Voors and his team had already been studying differences in markers of disease in the blood between men and women before the COVID-19 outbreak.
"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," Voors' colleague, Dr Iziah Sama, said.
The researchers measured concentrations of the enzyme in blood samples taken from two groups of heart failure patients from 11 European countries. There were 1485 men and 537 women in the first group. The second group, consisting of 1123 male participants and 575 women, were used to validate the findings discovered in the first group. The average age of participants in the first group was 69 for men and 75 for women, and 74 and 76 in the second group respectively.
When the researchers analysed a number of clinical factors that could play a role in concentrations of the enzyme, including a history of chronic obstructive pulmonary disease and the use of various drugs, they found the male gender was the strongest predictor of elevated ACE2 levels.
"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 in patients with cardiovascular disease. We found no evidence that ACE inhibitors and ARBs [drugs] were linked to increased ACE2 concentrations in plasma," Voors said.
"The effect of MRAs on ACE2 concentrations is not clear, as the weak increase in concentrations in the validation cohort was not seen in the index cohort. 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."
The enzyme is also found in the heart, kidneys and the tissues lining blood vessels, with particularly high levels in the testicals. The researchers think its presence in the testes may partially explain the higher concentrations in men - and why men are more vulnerable to COVID-19.
However, the researchers only measured ACE2 concentrations in plasma, not in tissues; concentrations of the enzyme in lung tissue is thought to be significant regarding viral infections, not ACE2 in the blood. This has been recognised as a limitation of the study.