Coronavirus and gender: Why are men more likely to die from Covid-19 than women

As of November 30, men accounted for more than three-quarters of deaths in Yemen, Bangladesh, Thailand, Malawi and Nigeria, and nearly as many in Afghanistan and Pakistan.

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18.12.2020. 18:18h

On January 2020, XNUMX, while little was known about a new mysterious respiratory disease that had emerged in Wuhan, China, geneticist Sharon Moalem tweeted a bold prediction of what lies ahead.

“Why are more men going to succumb to the newly discovered Wuhan Acute Respiratory Syndrome (VARS)?” asked Moalem, a 43-year-old Canadian living in New York with a long career researching rare genetic conditions over the past two decades.

His guess was correct.

According to the Global Health 50/50 database, far more men than women die from the effects of Covid-19 in most countries for which data is available.

Why will more males succumb to the newly discovered Wuhan Acute Respiratory Syndrome (WARS)? #TheBetterHalf https://t.co/7SxE4Fozpp
— Sharon Moalem MD, PhD (@sharonmoalem) January 20, 2020

As of November 30, men accounted for more than three-quarters of deaths in Yemen, Bangladesh, Thailand, Malawi and Nigeria, and nearly as many in Afghanistan and Pakistan.

In Turkey, Serbia, Kyrgyzstan and Hong Kong, that figure is approximately 62 percent.

Of the countries with the highest total number of deaths from Covid, the proportion of deaths among men was 64 percent in India and Mexico, 58 percent in Brazil and 54 percent in the US.

Data from the same database show, however, that the infection rate is similar in both sexes.

Then why are men disproportionately more affected by Covid-19 and what makes women more successful in surviving both diseases?

Strengthens resistance

Gender differences in survival are manifested at a very early age.

Globally, for every 100 women, 105 men are born. Women, however, have a higher chance of making it to their first birthday.

By the time they enter adolescence, women already make up more than half of their respective age group.

In every country, women live longer than men on average - six to eight years. For every man who lives to be a hundred, there are four women who have done the same.

"Women have always shown a higher survival rate in the long run. Covid-19 only underscores that," says José Eustachio Diniz Alves, a demographer who studies the deadly consequences of Covid-19 on the Brazilian economy and population.

"I would say it's the old normal," he tells the BBC.

But that is not all.

When it comes to resistance to disease, scientists have found that women have stronger immune systems and are less susceptible to certain types of cancer than men.

Additional evidence suggests that women are more resistant to cardiovascular disease and certain viral infections.

One study found that 57 percent of the 299 people who died in Hong Kong during the 2003 SARS epidemic, caused by a different type of corona virus, were men.

Men were also disproportionately affected by the Spanish flu of 1918.

What is the explanation for this disparity?

"better half"

Doctor Maolem is one of the most vocal proponents of the theory that, when it comes to survival, women are the stronger sex.

In his bestseller, The Better Half: The Genetic Superiority of Women, he lays out the evidence that women are biologically stronger than men, although behavioral patterns and lifestyles also play a role.

Women, for example, generally go to the doctor more regularly, smoke less and wash their hands more often.

In contrast, men are more prone to risky behavior and to allow their comorbidities to remain undetected.

Eustaquio Alves is among those who believe that the key to women's survival when it comes to Kovid-19 is most likely in a combination of factors.

"When it comes to mortality, biological factors explain less than social factors," he says.

Although he admits that attempts to explain why women are surviving this pandemic better are "almost certainly valid", Dr Moalem argues that we need to go further to find the real explanation.

"Those explanations overlook that the disproportionate toll that the coronavirus leaves on men is not an anomaly," he wrote in the New York Times in April.

"Instead, this could be a timely and compelling demonstration of what until recently was an underappreciated scientific fact: when it comes to survival, men are the weaker sex," he adds.

And he believes that everything is hidden in the way our genes are programmed to function.

The power of the X chromosome

In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46.

Twenty-two of those pairs look the same in both men and women. The difference is in the 23rd pair - sex chromosomes.

Women have two X (X) chromosomes, while men have one X and one Epsilon (Y) chromosome.

The X chromosome is structurally larger and more complex than the Y chromosome: it contains approximately 1.150 genes, long sequences of genetic material that produce essential proteins for cell function.

Chromosome Ipsilon, on the other hand, has between 60 and 70 genes.

But having two X chromosomes does not mean that women produce twice as much X protein.

For the life cycle, female cells choose only one X chromosome.

The second copy is randomly "silenced", a process known as X-deactivation.

Not every cell excludes the same X chromosome, which gives women an advantage.

If a man has a disease-causing gene on the X chromosome, there is a greater chance that the disease will manifest itself.

If a woman has the same disease, cells with a healthy copy of X will still express the genes correctly.

Although women will get sick, they are more likely to experience a milder form of the disease.

"Escape" from deactivation

Over the past 15 years, scientists have begun to better understand another process known as incomplete deactivation of the X chromosome.

This happens when genes are expressed from both active and inactive X chromosomes.

A study by researchers from the Institute of Molecular Medicine at the University of Helsinki, published in 2017, showed that incomplete deactivation of the X chromosome affects at least 23 percent of genes with that chromosome.

Although these genes are never fully expressed, as in active X chromosomes, this "escape" is enough to make a difference, helping women experience a milder form of genetic diseases.

Dr. Maolem says that these differences can not only explain women's longevity, but also explain why female babies born prematurely have a better chance of surviving in intensive care.

"Seeing the survival advantage for women at such a young age made a big impression," he tells the BBC, recalling his own experience in the neonatal intensive care unit 10 years ago.

Other factors

Other studies suggest that girls survive better in the neonatal intensive care unit because their lungs mature earlier.

This protects them from respiratory problems, one of the leading causes of death in the neonatal period.

But there are other factors that can help explain the differences between men and women - hormones, for example.

High levels of testosterone, the male sex hormone, are associated with risk-taking behavior and a weaker immune response after flu vaccination.

Estrogen, a female hormone, has anti-inflammatory properties and enhances immune reactions in the body.

Scientists are also investigating the role of a protein called angiotensin-converting enzyme 2, or ACE2, which enables the Sars-CoV-2 virus to enter the body and is located in the X chromosome.

Because women have two copies of the X chromosome and are therefore less affected by diseases associated with it, some scientists have suggested that this could be one explanation for why they are less affected by Covid-19.

Is gender a risk factor?

Since it first appeared, Covid-19 has proven to be much more than just a respiratory illness.

It can affect the cardiovascular system, kidneys, and even our sense of smell and taste.

But the explanation for all of the above remains a mystery.

Scientists say more study is needed to determine whether gender is a risk factor for Covid-19.

This would likely require sequencing the genomes of many more people who have developed severe and milder forms of the disease, and detective work to identify the genetic variations that would explain them.

Even then, other non-genetic factors, such as age, comorbidities, behavior and socio-economic conditions, especially poverty, would have to be taken into consideration.

After all, Covid-19 has affected groups of individuals both by the types of work they do and the conditions in which they live.

"A biological explanation of mortality from the virus would be interesting, but incomplete," says demographer Eustachio Alves.