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Early in February, Dr. Sabra Klein, a professor in the Department of Molecular Microbiology and Immunology of the Johns Hopkins Bloomberg School of Public Health, noticed a sex difference in COVID-19 infections based on reports emerging from China. She felt that men might have a greater risk than women of getting infected by the coronavirus causing the disease. But, in the U.S., there was no data at the time to validate her observation. Indeed, it wasn’t until late February that the Centers for Disease Control and Prevention confirmed the first case of community spread of COVID-19 in the country.

Two months later, by which point around 1.5 million Americans had been tested for the coronavirus nationwide, a large set of data showed that also in the U.S. a higher percentage of men have tested positive for the coronavirus than women: 23% of tested men were positive for the coronavirus, but only 16% of tested women were positive.

However, no one has the answer as to why men may be more vulnerable than women to the coronavirus. Several possible reasons have been suggested by medical experts and scientists, but none yet have an abundance of supporting laboratory or clinical data to back them up.

The unknown truth may now be gradually becoming revealed by the efforts of non-stopping research carried out around the world. The “window” opened by researchers to look into this biological puzzle is a human protein called angiotensin-converting enzyme 2 (ACE2), which has been demonstrated to allow the coronavirus causing COVID-19 to enter healthy human cells.

By measuring and comparing blood concentration of ACE2 in thousands of men and women from 11 European countries, researchers found that men have higher concentrations than women. Considering ACE2’s critical role in assisting the infection of the coronavirus, results from this study may provide an explanation as to why men are more vulnerable to COVID-19 than women.

However, many questions still remain, especially because of imperfections associated with the study—or at least its relationship with the coronavirus. First of all, each of the men and women whose blood ACE2 concentration were measured were patients with heart failure, and that prior medical condition may have been a deciding factor. Second, no one during the study was a COVID-19 patient as it was done before the coronavirus pandemic started. Also, only ACE2 concentrations in the blood were looked at in the study; the more important ACE2 concentrations in the lungs and other tissues were, unfortunately, not measured.

Thus, more worldwide research needs to be done before the truth can be fully revealed.

Regardless of its imperfections, data from this study still send out a clear alert to us. Biologically, men are more likely than women to become the weak defending point for coronavirus to break into families. All men—fathers, brothers, husbands and sons—should be more precautious and follow preventive guidelines more diligently: Always wear face masks when being outside, wash hands frequently and keep a minimum distance of six feet from others when possible in working places or public areas.

The results of this study, published in the European Heart Journal on May 10, has disclosed another important finding: Widely-prescribed drugs called ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) did not lead to higher ACE2 concentrations and should, therefore, not increase COVID-19 risk for people taking them. Patients with hypertension are positively impacted by this study: Previous concerns that using high blood pressure drugs, such as ACEIs or ARBs, may increase ACE2, and make patients prescribed them more vulnerable to COVID-19 infection, were proven wrong by this large-scale study.

If you are using ACEIs or ARBs to treat high blood pressure or other disease conditions, mention this pivotal study to your doctors, since the results add strong supporting evidences to the statement made by the American Heart Association on March 17 for not stopping the use of these drugs for anti-hypertensive therapy.  

References:

• The New Coronavirus Appears to Take a Greater Toll on Men Than on Women. https://www.npr.org/sections/goatsandsoda/2020/04/10/831883664/the-new-coronavirus-appears-to-take-a-greater-toll-on-men-than-on-women
• CDC Confirms Possible Instance of Community Spread of COVID-19 in U.S.
• US Death Toll Crosses 16,500; 11% Under 25 Years Testing Positive: White House.
• COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers. https://jamanetwork.com/journals/jama/fullarticle/2763803
• Circulating Plasma Concentrations of Angiotensin-Converting Enzyme 2 in Men and Women with Heart Failure and Effects of Renin-Angiotensin-Aldosterone Inhibitors. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa373/5834647
• Men Have High Levels of Enzyme Key to COVID-19 Infection, Study Finds. https://www.reuters.com/article/us-health-coronavirus-ace2-men/men-have-high-levels-of-enzyme-key-to-COVID-19-infection-study-finds-idUSKBN22M0UA
• Don’t Stop ACE, ARB Drugs Over COVID-19 Concern, Groups Urge. https://www.medpagetoday.com/infectiousdisease/COVID19/85817
• COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers—What Is the Evidence? https://jamanetwork.com/journals/jama/fullarticle/2763803
• American Heart Association. HFSA/ACC/AHA Statement Addresses Concerns re: Using RAAS Antagonists in COVID-19. https://professional.heart.org/en/science-news/hfsa-acc-aha-statement-addresses-concerns-regarding-using-raas-antagonists-in-covid-19