Here's Another Explanation for Why Men May Be More Vulnerable to Serious COVID-19 Illness

May 10, 2020
Peter Wehrwein
Peter Wehrwein

Men have higher concentrations of ACE2 in their blood.  

The COVID-19 gender differential is pronounced, with men much more likely to suffer serious consequences from the disease than woman.

Chinese researchers published findings in Frontiers in Public Health in late April showing that the prevalence of COVID-19 among men and women was about equal but that number of men who died from the disease was 2.4 times higher than it was among women.

CDC mortality data, based on death certificates, don’t show such a strong skew towards males. Still, roughly 56% of the COVID-19 deaths were among males, according to data that was available early in May, so the differential is still there.

Everything from the tendency for men to have underlying health conditions to women having immune responses that are more effective against the disease has been offer as an explanation for the COVID-19 gender differential.

Now evidence published in tomorrow’s European Heart Journal points to another explanation. Findings from a large group of roughly 2,000 heart failure patients that were validated in a second group with slightly fewer patients show that men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in their blood than women.

Because ACE2 enables SARS-CoV-2, the virus that causes COVID-19, to infect healthy cells, the higher concentrations could be another reason men are more vulnerable to serious cases of COVID-19 than women, according to the reseachers.

But as a press release about the study points out, this study measured ACE2 concentrations in the blood, not in people's tissues, and it is believed that it it is ACE2 in lung tissue, not in the blood, that is important to SARS-CoV-2 infection. 

The researchers who conducted this study also found that heart failure patients taking ACE inhibitors or ARBs did not had higher concentrations of ACE2 in their blood. An accompanying editorial by Gavin Oudit, M.D., Ph.D., FRCPC, of the University of Alberta, Canada, and Marc Pfeffer, M.D., Ph.D., of Harvard-affiliated Brigham and Women’s Hospital, said this study offers “supporting evidence to continue ACE inhibitors or ARBs in patients at risk for SARS-CoV-2 infection.”

Oudit and Pfeffer also mention two observational studies of hospitalized COVID-19 patients that suggest there might be even be a protective effect against COVID-19 from ACE inhibitors and ARBs.

Adriaan Voors, M.D., Ph.D., of the University Medical Center Groningen in the Netherlands, and his colleagues were studying differences in biomarkers in the blood between men and women before the COVID-19 pandemic, according to the press release.

“When we found that one of the strongest biomarkers, ACE2, was much higher in men than in women, I realized that this had the potential to explain why men were more likely to die from COVID-19 than women,” said Iziah Sama of the University Medical Center Groningen, the lead author, according to the press release.

The researchers measured ACE2 concentrations in blood samples taken from two groups of heart failure patients from 11 European countries. The first group comprised 1,485 men and 537 women. Findings from that group were validated in a second one that comprised 1,123 men and 575 women. The median age of the participants of the first group was 69 years for men and 75 years for women. In the second group, it was 74 and 76 years.