Why does Covid-19 kill more men than women?

A vicious fever, terrifying bouts of shortness of breath and excruciating headaches – all culminating in a dash from 999 to Edinburgh Royal Infirmary, emergency oxygen and intravenous fluids in an isolation room.

For Scott Dixon, suffering from Covid-19 was a frightening ordeal. “The memory will never leave me,” he says.

It is also a state in which he never thought he would find himself.

Just before his 50th birthday, Scott is fit and healthy, rarely suffering as much as a cold. He is not overweight, exercises regularly, and has none of the underlying risk factors that would have made him an obvious candidate for a serious illness.

Aside from one, that is – he’s a man. A growing body of evidence now suggests that men are affected by the virus much more often.

Although infection rates between men and women seem similar – based on positive tests – men are more likely to end up in intensive care and die much more often.

Scott, who is now recovering at home, notes with some surprise that “all the other patients in the ward were men.”

The story of Mark and Kathy Anders, both 57, from Rugby in Warwickshire is another strong example. The couple developed mild flu-like symptoms four weeks ago. While Kathy, a family doctor’s secretary, recovered after two weeks, the condition of paramedic Mark – a fit non-smoker – deteriorated and he suffered from relentless fever of almost 40C.

Last Friday, he was rushed to the hospital for emergency treatment. “He was not getting any better and he had developed a painful chest pain every time he inhaled,” said Kathy, who now isolates himself at home.

“First he was taken to an acute department, but he deteriorated quickly. Scans showed traces of Covid-19 on his lungs and he had pneumonia.

“On Sunday I received a call from him saying,” I think they will take me to intensive care tomorrow – and I don’t think I will come out. “

But in a remarkable turnaround, doctors got Mark’s temperature under control and were able to control his breathlessness with supplemental oxygen within 24 hours.

“So far he has avoided intensive care, but we have been told that if his condition worsens further, he has no choice,” says Kathy.

Unlike Mark, Kathy was unable to take a test, but she has no doubts about her diagnosis.

She says, “We are NHS employees, so we are exposed to infected patients. We got sick within days of each other. Although my symptoms were mild, I have never felt anything like it. ‘

And no one is more surprised by how different their bodies have been than Kathy.

“I was convinced that if we got it – and suffered hard – it would be me,” she says.

“I’ve been treated twice for cancer and I’m the one who picks up bugs, while Mark rarely catches a cold.”

This experience is known across the country. As cases of Covid-19 increase, a surprising report from the Intensive Care National Audit & Research Center (ICNARC) shows that men make up 73 percent of the more than 2,000 most critically ill patients admitted to intensive care units.

The results for these patients between 52 and 70 years old are not yet known, as many remain in the hospital. But this is not just a British phenomenon. Global Health 50/50, a campaign for equality between men and women, collects information on cases of coronavirus in men and women.

So far it has reliable figures from 18 countries. The proportion of men and women who test positive for Covid-19 remains roughly the same for each. But overwhelmingly more men are dying.

In Greece and Peru, 72 percent of people who died with the virus are men. In Italy, 68 percent of the deaths were men and 64 percent each in China, Denmark and Germany.

UK data has not been updated since late March. However, it also seems to reveal the same grim picture – 61 percent of the more than 6,000 deaths are men.

The data is currently incomplete. Significant numbers of deaths in nursing homes – whether with confirmed coronavirus or suspected infections – have not yet been included in official figures, with a delay of approximately 17 days.

Industry Body Care England has said that the death toll in homes could already be close to 1,000, including many vulnerable and older women. So it is likely that the number of deaths among women in this country is underestimated.

But the Global Health 50/50 report does conclude that men are between 50 and 80 percent more likely to die than women after a coronavirus diagnosis.

So the obvious question is why?

The discrepancy was first noted in China, the origin of the pandemic. An analysis of 44,672 confirmed cases through February 11 found that the death rate among men was 2.8 percent, compared to 1.7 percent among women.

At the time, some experts wondered if lifestyle factors were to blame. In China, 50 percent of men smoke, compared to less than four percent of women.

Smoking, as is known, increases the risk of lung and heart disease, high blood pressure and cancer, increasing the risk of severe Covid-19.

But the statement did not hold out when the virus moved to Western countries. In Europe, the smoking rate is lower – an average of 29 percent, according to the World Health Organization. And while men are still using cigarettes more often, there are also high smoking rates in women.

Something else had to be involved. In fact, men have long been known as the frailer gender when it comes to viruses.

It was the same picture with SARS – another coronavirus that spread around the world in 2003. It is known to have killed only 780 people worldwide, while Covid-19 has already led to more than 90,000 deaths. But SARS was also disproportionately more deadly in men – 21 percent of the infected men died, compared to 13 percent of the women.

In 2012, 63 percent of those infected with the MERS coronavirus were also men.

“This is a pattern we’ve seen with many viral respiratory infections – men may have worse results,” says Sabra Klein, a scientist who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “We’ve seen this with other viruses. Women fight them better. ‘

Dr. James Gill, locum family doctor and honorary clinical teacher at Warwick Medical School, believes that one reason is that men “just don’t take good care of their bodies” and drink more alcohol on average.

Studies suggest they are less likely to follow healthy diets or seek medical attention if they need it.

As a result, men are more likely than women to suffer from chronic conditions such as heart and lung disease, cancer, high blood pressure and type 2 diabetes – all of which can lead to more serious coronavirus symptoms.

Other studies have shown that men are less likely to wash hands and use soap or to adhere to health advice. In theory, this could mean ignoring social distance policy, although there is no direct evidence to support it.

Immunologist Professor Philip Goulder of the University of Oxford says these are important gender differences in behavior that “have a huge impact on the outcome of infections such as coronavirus.”

There is also an ongoing debate as to whether obesity on its own, rather than as a contributing factor to high blood pressure and diabetes, increases the risk of coronavirus problems. The 2017 Health Survey for England found that men are more likely to be overweight or obese than women (67 percent compared to 61 percent). The most recent ICNARC data do not suggest that people with a Body Mass Index higher than 25 are more likely to require hospital treatment with coronavirus than people of healthy weight.

But those who are obese are more likely to die of critical care.

Based on the more limited data available on the outcomes, 57 percent of people with a BMI over 30 died, compared to 43 percent of people with a normal BMI.

Duncan Young, professor of Intensive Care Medicine at the University of Oxford, says: ‘The numbers are small, but there appears to be an increased risk of death in obese patients admitted to an intensive care unit with a Covid-19 -infection.’

Dr. Gill says that a plausible theory is that in men, the way their weight is distributed can have an effect.

“In general, men have an apple-shaped weight distribution, which means fat is spread more widely across their torso,” he says. “It can put extra pressure on the breathing muscles, which work harder if you carry more weight. You deteriorate faster. It doesn’t matter what put a patient in breathlessness in the first place.

“Huge amounts of evidence from anesthesiology and general surgery tell us that if you’re obese, your results are worse on a ventilator.”

Can there also be a genetic explanation for inequality? Scientists walk through DNA databases to find out why some people are more susceptible to the worst devastations of the disease than others.

But some already believe that fundamental differences between male and female immune systems can be a key factor.

Prof Goulder: “It is increasingly recognized that there are substantial differences in the immune system between men and women, and that they have a significant impact on the outcome of a wide range of infectious diseases.

“The lifelong immune response to vaccines and infections is typically more aggressive and effective in women than in men.”

At the core of every cell is genetic material called DNA wrapped in thread-like structures called chromosomes.

These contain sequences of “code” called genes that determine how cells function and, as a result, everything from hair and eye color to blood group.

The usual number of chromosomes in each cell in the body is 46 – or 23 pairs.

We inherit half from our mother and half from our father.

One pair is known as sex chromosomes, and they determine whether a person is born male or female. The sex chromosomes in men and women differ in structure: women have two that, when viewed under an extremely powerful microscope, have the shape of an X. Men have one in the shape of an X and one in the shape of a Y.

There are a number of critical immune genes on the X chromosome, says Prof. Goulder.

Since women have two copies of this chromosome and men have only one, it means women are better equipped to fight infections and viruses.

When it comes specifically to coronavirus, there is a protein called TLR7 – again, on the X chromosome – that detects the Covid-19 infection.

This triggers a signal that results in the production of chemicals in the body called inferons. These “essentially have direct antiviral effects, but also enhance the innate immune response,” said Prof. Goulder.

“It’s about recognizing a threat and generating a response. The more TLR7 receptors you have, the better that response. ‘

Men, who have only one X chromosome, therefore naturally have fewer TLR7 receptors to fight the coronavirus.

At first glance, this may seem like a huge biological mistake. But Prof. Goulder explains that this may have had an evolutionary advantage.

In theory, it is more important that women, who should bear and raise children, be able to fight infections, including viruses, and stay healthy.

Historically, other evolutionary roles, such as partner attraction and physical strength, were more favorable for men.

The early man just didn’t need as strong an immune system as women, he says.

Other factors include sex hormones such as testosterone, which suppresses the immune system.

Testosterone is often known as the male sex hormone because it is responsible for sperm development, although women also produce small amounts.

“There is a very good study of the response to the influenza vaccine in men and women,” says Prof. Goulder.

“The women had higher antibody responses than the men, but the women with the lowest testosterone had the highest and the worst response was seen in men with the most testosterone.”

Whether testosterone levels can also affect the severity of the coronavirus remains to be investigated.

Now, the great hope to clarify the difference between the effects of coronavirus in men and women will come from the proposed roll-out of antibody tests.

No test has yet been proven reliable.

Positive tests for coronavirus seem to show that men and women are about as likely to become infected – 52 percent compared to 48 percent.

But an antibody test with sections of the population could reveal the truth, including whether women are more likely to be carriers, develop only mild symptoms, or develop a stronger antibody response than men.

Perhaps proof that flu in men may not be a myth after all.