Blood Yields Clue to Why COVID-19 Is Tougher on Men

Since the coronavirus pandemic began, rates of hospital admission and death from COVID-19 have been significantly higher in men than women.

Now, new Dutch research suggests a reason why: Compared to women, men have higher concentrations of a blood enzyme that helps the new coronavirus infect human cells.

The enzyme is called angiotensin-converting enzyme 2 (ACE2).

“ACE2 is a receptor on the surface of cells,” explained lead researcher Dr. Adriaan Voors, a professor of cardiology at the University Medical Center Groningen, in the Netherlands. His team published their findings May 11 in the European Heart Journal.

ACE2 “binds to the coronavirus and allows it to enter and infect healthy cells,” Voors explained in a journal news release. “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.”

Because of the importance of ACE2 in heart failure, the Dutch team was already exploring the enzyme’s role in cardiovascular health long before the new coronavirus appeared on the scene.

In their study, the researchers tracked ACE2 concentrations in the blood of almost 1,500 men and more than 500 women. All were older people treated for heart failure at medical institutions in 11 European countries.

In a long list of possible factors that might influence ACE2 concentrations in the blood, being male was the strongest factor, the researchers said.

The study may also have implications for people who are taking common heart medications.

Because of their links to ACE2, doctors have worried that common heart medicines, such as ACE inhibitors or angiotensin receptor blockers (ARBs), might increase risks for patients battling COVID-19. But the new study found no links between ACE2 blood levels and the use of these drugs.

So, “our findings do not support the discontinuation of these drugs in COVID-19 patients, as has been suggested by earlier reports,” Voors noted.

His team stressed, however, that they only tracked levels of ACE2 in liquid blood, not tissues such as lung tissue, so they cannot yet provide a definitive answer on whether ACE inhibitors or ARBs are harmless in people with COVID-19. The patients studied did not have COVID-19 at the time, the researchers added.

As to why ACE2 levels are higher in men than women, the study authors said that the enzyme is regulated in men in the testes, so that could explain its higher concentrations in males.

Two U.S. heart experts said the findings have real merit.

Most importantly, “heart failure patients should consult their cardiologist before changing any medicines as they relate to the possible increase in [coronavirus infection risk],” said cardiologist Dr. Satjit Bhusri. He practices at Lenox Hill Hospital in New York City.

Dr. Geurys Rojas-Marte specializes in the treatment of advanced heart failure at Staten Island University Hospital, also in New York City. He said that “ACE2 is a normally occurring enzyme in the body that plays an important role in regulating the blood pressure. The enzyme is abundant in the lungs, heart, kidneys and blood vessels. It is also shed into the plasma and that is why we can measure it.”

Rojas-Marte said that although the Dutch group only theorized that ACE2 concentrations in lung tissue would be similar to those seen in blood, their theory is “a good one in my opinion.” Still, more study is needed, he said.

As to the pros and cons of using certain heart medicines while the new coronavirus is circulating, Rojas-Marte pointed to a study published recently in the New England Journal of Medicine. That research involved “more than 8,000 patients,” he said, and “showed no difference in mortality in patients affected by COVID-19 previously taking ACE inhibitors or ARBs.”

More information

Look to the U.S. National Library of Medicine for more on heart failure medicines.