Men’s blood contains large concentrations of an enzyme that helps SARS-CoV-2 coronavirus infect cells.
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The results of a large study conducted by scientists from the University Medical Center Groningen (Netherlands) and their colleagues on several thousand patients show that in men the concentration of angiotensin-converting enzyme 2 (ACE2) in the blood is higher than in women. Since it is ACE2 that allows coronavirus to infect healthy cells, the difference in its concentration may explain why men are more vulnerable to Covid-19. An article about this is published in the publication. European heart journal.
The limitations of the work do not yet allow us to draw unambiguous conclusions about the causal relationship between the course of coronavirus infection and plasma ACE2 concentrations, however, they help to build assumptions that can be further verified.
ACE2 is a receptor on the surface of cells. SARS-CoV-2, the causative agent of the current pandemic, binds to it, which allows it to penetrate into healthy cells and infect them after the enzyme has been modified by another protein on the cell surface called TMPRSS2. High levels of ACE2 are present in the lungs – therefore, it is believed that they play a crucial role in the progression of lung diseases associated with Covid-19.
Researchers began to study the differences in blood disease markers in men and women before the coronavirus outbreak. After the outbreak of the pandemic, they used the previous data to examine their relationship to possible causes of gender differences during the Covid-19. “When we found that one of the strongest biomarkers, ACE2, was much higher in men than in women, I realized that this could explain why men are more likely to die from Covid-19 than women,” says one of the authors of the work, Dr. Isiah Sama.
Scientists measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 different European countries. In the first group (the index cohort, on which the hypothesis was initially tested), there were 1485 men and 537 women. Then the researchers confirmed their results on the members of the second, control group, consisting of 1123 men and 575 women. The average age of participants in the index cohort is 69 years for men and 75 years for women, and in the control – 74 and 76 years, respectively.
When researchers examined a number of clinical factors that may play a role in ACE2 concentrations, including the use of inhibitors of this receptor, as well as a history of chronic obstructive pulmonary disease, coronary artery disease, and atrial fibrillation, they found that male sex was the strongest predictor of elevated concentrations of angiotensin-converting enzyme in organism.
This protein was found not only in the lungs, but also in the heart, kidneys and tissues lining the blood vessels, and especially high levels were in the testes. Researchers suggest that its regulation in the testes may partially explain higher ACE2 concentrations in men and why they are more vulnerable to Covid-19.
Among other things, these works showed that in patients with heart failure taking some medications for this disease, the concentration of ACE2 in the blood was not excessive. These “protective” properties turned out to be endowed with drugs aimed at the renin-angiotensin-aldosterone (RAAS) system, for example, ACE inhibitors or angiotensin receptor blockers (ARBs).
Dr. Adrian Voors, who led the group, notes: the results indicate that it is better to study how taking these drugs can affect the condition of patients with heart failure infected with coronavirus. Some recent studies have shown that RAAS inhibitors can increase the concentration of ACE2 in plasma, thereby increasing the risk of infection with Covid-19 in patients receiving them.
New work shows that this may not be the case, but further research is needed to consider not only the concentration in the plasma, but also in the tissues: this is a more important and accurate indicator of risk. In addition, the abolition of these drugs seriously increases the risk of death for patients with heart failure – from the current disease; in this case, the attending physician must also weigh the probability of death due to coronavirus infection.
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