Why do more men die from COVID-19?

Since the beginning of the pandemic, many possible reasons have been put forward as to why men tend to suffer more when they become infected with the novel coronavirus: Men pay less attention to their health, smoke more or eat less nutritiously. According to such theories, the older generation in particular has an unhealthy lifestyle. And in addition, men generally wait longer before seeing a doctor.

Now, a new meta study published December 9 in the journal Nature Communications confirms earlier research findings. 

Data gathered in more than 20 countries by the research initiative Global Health 50/50 had already confirmed in June that women are infected with the virus as frequently as men. But men are more likely to contract severe forms of COVID-19 and die from the infection. The ratio of mortality according to sex is about one-third to two-thirds.

One factor is certainly the greater prevalence of particular preexisting conditions in men. For example, men suffer much more often from cardiovascular diseases, from which they also die more often than women.

Another decisive factor is the age structure. According to Germany's Robert Koch Institute (RKI), at least twice as many men as women have died in all age groups up to the 70 to 79 age group. Even the RKI is unable to name the reasons for this gender difference.

ACE2 receptor as the major gateway?

The ACE2 receptor might play an important role because it serves as a kind of gateway for the diseases COVID-19, SARS and MERS, which are all caused by coronaviruses. Men were also more affected by MERS, said  Bernhard Zwissler, Director of the Department of Anaesthesiology at the LMU Clinic in Munich in June of this year.

According to a study by the University Medical Center Groningen, this ACE2 receptor is found in higher concentrations in men. Researchers discovered this gender difference while investigating a possible correlation between the ACE2 receptor and chronic heart failure.

According to Zwissler, researchers are currently investigating whether the administration of ACE inhibitors as antihypertensive drugs leads to the increased formation of the ACE2 receptor in cells, making them more susceptible to infection. He says this is certainly conceivable but that nothing has been proven as yet.

Estrogen and a stronger immune system

The female immune system is also more resilient than that of men. The main reason for this is the female sex hormone estrogen. It stimulates the immune system so it acts faster and more aggressively against pathogens. The male hormone testosterone, on the other hand, inhibits the body's own defenses.

According to virologists, the generally faster and stronger reaction of women's immune systems to viral infections is also evident in the case of other viral diseases, such as influenza or even simple colds. This would seem to indicate that jokes about "man-flu" have a grain of truth to them.

On the other hand, women suffer more often from autoimmune diseases, in which the immune system overreacts and attacks body cells — a possible complication with COVID-19 as well.

There are also "genetic reasons" that favor women, the molecular virologist Thomas Pietschmann told DW. He says that "some immune-relevant genes, for example genes that are responsible for recognizing pathogens, are encoded on the X chromosome. Because women have two X chromosomes and men have only one, the female sex has an advantage here."

India as an exception

Surprisingly, research from India shows that women there have a higher risk of dying from COVID-19 than men. It shows the mortality rate for infected women in the country as being 3.3% overall, while the rate for infected men is 2.9%. In the 40-to-49 age group, 3.2% of infected women died, compared to 2.1% of men. In the 5-to-19 age group, only women and girls died.

The reasons why India should be an exception are currently being closely scrutinized. It is suspected that women are more affected, among other things, because there are simply more older women than men in India.

In addition, research has suggested that in India less attention is paid to women's health in comparison with men's. Accordingly, women visit the doctor less frequently and often try self-medication first. They also tend to be tested or treated comparatively late.

"How much of this can be attributed to biological factors and how much of this is associated with social factors is unclear. Gender can be a critical factor in Indian settings," SV Subramanian, Professor of Public Health at Harvard University, told the British broadcaster  BBC.

The Spanish flu of 1918 killed significantly more women than men in India. Women were more susceptible to the infection as many of them were malnourished, they were often locked up in unhygienic and poorly ventilated apartments and because they were much more likely than men to care for the sick.

Children less at risk

Surprisingly, children are not among the weakest members of society when it comes to the new coronavirus — in most children, the disease it causes takes a comparatively mild and often asymptomatic course. Of the around 9,000 people who have died of COVID-19 in Germany since the beginning of the pandemic, only three were under 18 years of age.

The reason for this is not yet fully understood. Doctors assume that the already innate "unspecific system" is effective in small children. As protection against the first pathogens, the mother gives her own specific immune protection to the fetus and later to the newborn via breast milk.

This innate immune defense includes, for example, scavenger and killer cells — white blood cells that attack all pathogens that enter the body via the mucous membranes or the skin.

This "passive immunization" usually lasts until children have built up their own defense system. Children develop their specific immune defense up to the age of about 10. And even after that, their defense system remains capable of learning throughout their lives when new pathogens appear.

Children are not spreaders

In any case, the age distribution of COVID-19 cases differs significantly from that of other infectious diseases, where children are often considered "super-spreaders" because they spread a virus quickly throughout the population.

This is not the case with the new coronavirus, according to a much-noticed study commissioned by government of the German state of Baden-Württemberg. The study is now serving as the basis for a rapid and comprehensive return to normal operations in daycare centres and schools, provided that hygiene standards and distancing rules are observed.

But it remains unclear whether infected children are just as contagious as infected adults. In another much-discussed study, the virologist Christian Drosten from the Charité Hospital in Berlin showed that children have just as many viruses in their throats as adults. Other international studies have also come to this conclusion.

However, a strong presence of viruses in the respiratory tract does not prove that these viruses are passed on equally. Since children have fewer symptoms — for example, less coughing — it could be that they themselves are infected but that they infect fewer other people, pediatricians and hygiene specialists said in a statement issued by four medical associations.

This article from June 26, 2020 was last updated December 17, 2020 based on a new meta study in the scientific journal Nature Communications.