Coronavirus “burns” men more. Scientists have an explanation

Men have a much worse prognosis for coronavirus infection and the course of COVID-19 than women. Both lifestyle and lead are responsible for this, as well as a combination of factors such as genetic strain and the action of sex hormones. Scientists want to use this knowledge to develop a more effective treatment for covid patients.

1. The researchers found that men are more likely to be infected and severely affected by the coronavirus than women. This applies to both SARS-CoV-2 and other viruses from the coronavirus family, e.g. MERS or SARS-CoV-1
2. The reasons include: lifestyle factors such as smoking and hygiene
3. However, genetic factors also come into play. Important genes for the immune system are found on the X chromosome, which is duplicated in women
4. The differences in the immune response in men and women also result from the action of sex hormones. Testosterone helps the immune system to a lesser extent than female estrogen
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Author: Gerlinde Felix / The World

Coronaviruses don’t like men?

There is one (in) pattern in a pandemic: Men who contract the coronavirus are more likely to develop COVID-19 more severely than women. The risk of death is also much higher in their case. «As far as coronaviruses are concerned, this relationship has already been recognized in relation to MERS and SARS-CoV-1. In the case of SARS-CoV-2, it was first noticed during the first wave of infections in China, the USA, Germany and Italy »says Andrea Kröger, professor of molecular microbiology at Otto von Guericke University in Magdeburg.

After five waves of coronavirus, the numbers are clear: the risk of dying from COVID-19 depends not only on age but also on gender. In Germany, about 2,37 times more men in the 35-59 age group die of this cause than women. This value is somewhat in line with age: 60 times more men than women die among people between the ages of 79 and 1,88. Over the age of 80, the rate drops to almost 1,5, but more often than not, males experience significantly less of the pandemic.

1. Also read: Men and women react differently to coronavirus infection

Hygiene, cigarettes and immunity

There are many possible reasons for this. It is said that men care less about hygiene than women. They also have a higher proportion of smokers, which increases the risk of conditions such as diabetes and cardiovascular disease. Obesity is a risk factor for COVID-19, which may also have a negative impact on the course of the infection.

But are these relationships sufficiently clear to explain the large variations in the course of the disease and the risk of dying from COVID-19? “Unlikely. Differences are also due to the different immune responses of men and women to viruses and bacteria, as well as variables that help determine the appropriate immune response»Says Andrea Kröger.

1. see also: Men may be more susceptible to coronavirus infection because of a specific enzyme in the lungs

The rest of the text below the video.

Women are stronger – it’s a matter of evolution

To explain this, it is good to look at human evolution. Women need a particularly strong immune system to protect unborn babies and infants from infectionsfor example by breastfeeding. Strong body defense served to preserve the species.

This can be easily explained thanks to molecular biology. The immune system consists of innate and acquired immunity, which work closely together in the immune response. The innate immune system is responsible for a quick, all-round attack after an infection. It works according to a fixed schedule: in a few minutes the cells neutralize as many “invaders” as possible and then sound the alarm to summon more immune cells from the blood to help. Within a few assets

1. Check it out: How does the immune system work?

But what does this have to do with gender? This is where the X and Y chromosomes come into play. Males have the X and Y chromosomes in the nucleus of their cells, and females have two X chromosomes, one from the mother and one from the father. Some very important genes for the immune system are found on the X chromosome. In each cell, one X chromosome is active and most of the other is not. However, it is difficult to determine which X chromosome is active and which is partially mute – it changes from cell to cell.

“Therefore, defective genes can be compensated for as long as the gene is not present in both X chromosomes simultaneously in the defective version,” explains Kröger. Some of them are not fully silenced, and among them are genes very important for the functioning of the immune system, such as the toll-like receptor 7 (TLR7).

1. Check it out: COVID-19 Coronavirus in Women. Scientists suggest that women are more dangerous carriers of the coronavirus

One receptor is crucial

TLR7 is part of the innate immune system and can recognize certain structures such as single-stranded genetic material, i.e. SARS-CoV-2 ribonucleic acid (RNA). ‘The TLR7 receptor in immune cells can use type 1 interferons to set off an alarm,’ explains Kröger. Interferons are immune-stimulating, antiviral proteins.

Known viruses, including SARS-CoV-2, can inhibit or at least weaken interferon formation. “While in men hardly any interferon reaches neighboring cells, women have the advantage that some interferons actually penetrate them,” says Andrea Kröger.

Since the TLR7 receptor gene is active on both X chromosomes, the female has more TLR7 receptors than the male. “This is why For example, the female immune system can recognize coronaviruses better and faster than the male immune system and trigger a much stronger and faster interferon response. Women’s immunity is activated faster«.

There are also other differences in the immune response between men and women. Women who are infected with viruses and bacteria also produce more antibodies and these persist longer than in men. In addition, they generate stronger T-cell defense in the event of infection, which reduces the risk of severe COVID-19.

The immunologist Akiko Iwasaki at Yale University discovered this mechanism in 2020. Instead of a strong T-cell response like women do, men have elevated levels of certain pro-inflammatory messengers. At the first sign of inflammation or infection, these immune cells rapidly migrate into the tissue to find pathogens there, absorb them, and eliminate them through digestion.

Akiko Iwasaki and her research team found two things: women tend to produce less inflammatory transmitters immediately after infection, which is more severe in those with high blood levels. Apparently, a strong T-cell response isn’t good for women – and maybe not for men either.

Estrogen stimulates immunity better than testosterone

Sex hormones also affect how men and women deal with infectious diseases differently. It has long been known that testosterone, estrogen and progesterone interact with and activate immune cells. Therefore, in women, the ability to ward off malignant microbes also changes during the menstrual cycle with estrogen levels. Especially at the beginning of an infection, estrogen helps to stimulate the female immune system and trigger a strong T-cell immune response.

The dominant sex hormone in men helps the immune system to a lesser extent: triggers more pro-inflammatory responses, causing the immune system to overreact. This mechanism has been linked to lung destruction in COVID-19.

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A study by American doctors also shows how complex these connections are. The conclusion is that even low testosterone levels are not good for men. «Men with COVID-19 who were not initially seriously ill but had low testosterone levels were more likely to need intensive care or intubation two to three days later«Reports lead author of the study, Sandep Dhinds of Washington University in St. Louis. It is also related to the fact that the fat around the abdominal organs produces and releases large amounts of pro-inflammatory substances.

The link between sex hormones and the immune response to SARS-CoV-2 has raised hope among some doctors in the United States that it will be possible to support the immune response in men with temporary estrogen or progesterone intake, thereby reducing the risk of severe COVID-19. Therefore, in April 2020, a clinical trial began at the Renaissance School of Medicine at Stony Brook University, Long Island, and at Cedars-Sinai Hospital in Los Angeles. The results are still pending, but the administration of hormones does not seem to produce any spectacular effects so far.

Similar studies were conducted in women. Their hormonal status changes with age – and the immune system works less efficiently. «Especially in women, the entire innate immune system becomes slowed down, which means less active. This also includes pattern recognition receptors such as the toll-like 7 receptor. Since the related gene is transcribed less frequently, less TLR7 is produced. This weakens the interferon alarm system, »says Kröger. Not surprisingly, the risk of death for women around the age of 60 increases.

Hormone therapy in the treatment of COVID-19

Since the quality of the female immune response is so strongly dependent on estrogen, the question arises whether hormone therapy with a synthetic form of the natural female sex hormone estrogen, estradiol, can have a positive effect on the course of any COVID-19 and lower the risk of death.

Researchers at the University of Southampton and the University of Oxford studied this in a cohort study. Result: women who received hormone replacement therapy experienced less severe course of COVID-19 than those who had not corrected the hormone deficiency. The research results have yet to be independently verified. However, the authors point out that long-term hormone replacement therapy is not suitable as protection against coronaviruses as it increases the risk of breast cancer.

In medicine in general, more attention should be paid to the strong differences in the immune system, the researchers say. According to Kröger, people cannot be dumped together. “First you have to distinguish between men and women and then look at each gender individually,” she says.

The problem became apparent 30 years ago when the World Health Organization (WHO) hastily phased out a new measles vaccine in 1992 after clinical trials showed that it led to increased mortality among young girls in Senegal and Haiti. The boys didn’t get hurt. To this day, it is not clear why this happened.

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