Immune response could explain why coronavirus hits men harder

Men may be more likely to suffer severe cases of coronavirus or die of the disease because they have weaker immune responses, a new study suggests.

Researchers found that male patients had poor production of certain types of immune cells that kill the virus and fight off inflammation.  

However, women’s immune systems had a robust response that did not decrease with age as seen in men.

The team, from Yale University, in New Haven, Connecticut, says the findings offer some clues in the differences between the sexes and add that men and women may need separate types of vaccines and treatments.  

In an effort to understand why this occurs, scientists at Wake Forest School of Medicine conducted a review of data on hormone activity, especially oestrogen

A new study from Yale University found that male coronavirus patients tended to have high levels of pro-inflammatory proteins called cytokines early in the infection, which can lead to deadly cytokine storms. Pictured: Navy soldiers conduct check-in procedures on an incoming COVID-19 patient at Javits New York Medical Station, April 5 

The enzyme is more prevalent in men due to the lack of oestrogen keeping numbers down - which could account for why symptoms are worse in men, the team said

Women tended to have a stronger production of T-cells, which are white blood cells that bind to and kill viruses. Pictured: A COVID-19 patient is attached to a ventilator in the emergency room at St Joseph’s Hospital in Yonkers, NY, April 20

‘We now have clear data suggesting that the immune landscape in COVID-19 patients is considerably different between the sexes and that these differences may underlie heightened disease susceptibility in men,’ said senior author Dr Akiko Iwasaki, a professor of immunology at Yale University School of Medicine, in a statement.

‘Collectively, these data suggest we need different strategies to ensure that treatments and vaccines are equally effective for both women and men.’  

Around the world, men account for about 60 percent of deaths from COVID-19, the disease caused by the virus. Individual countries have also reported similar circumstances. 

In the UK, researchers studying 17 million adults found that men could face nearly twice the risk of death from the virus as women. 

And data out of China, where the crisis started, showed that at least two-thirds of patients who died were male.

However, why the male population has been hit harder has been unclear.

For the study, published in the journal Nature, the team looked at 17 men and 22 women admitted to Yale-New Haven Hospital between March 18 and May 9, and who had tested positive for coronavirus.

Male patients (in yellow) tended to have weak T-cells responses, which only worsen with age, a process that doesn't occur in women

Male patients (in yellow) tended to have weak T-cells responses, which only worsen with age, a process that doesn’t occur in women

Iwasaki told The New York Times that patients on ventilators or on medications that affect the immune system were excluded ‘to make sure that we’re measuring natural immune response to the virus.’

Researchers collected nasopharyngeal swabs, blood, saliva, urine and stool, every three to seven days as well as from non-infected control subjects. 

Results showed neither differences in viral load between men and women nor in levels of coronavirus antibodies. 

However, in the early stages of infection, male patients tended to have more inflammatory proteins called cytokines than female patients.

Cytokines are generally launched by the immune system as a first line of defense, arriving at the infection site and creating inflammation as physical barrier against the virus to promote healing.

In patients with COVID-19, these proteins are known for a dangerous overreaction by the body called a cytokine storm.

These so-called storms occur when the body doesn’t just fight off the virus but also attacks its own cells and tissues. 

Cytokine storms can trigger respiratory distress, which can lead to multi-system organ failure and death.

The high concentration of cytokines that male patients experience early on in the infection make these end results more likely. 

Researchers found that women tended to produce more and stronger T-cells, a type of white blood cell that binds to and kills virus-infected cells.

Men, however, had a less robust T-cell response than women, and it was linked to the severity of their illness. 

Additionally, the older menwere, the weaker their T-cell weres. But this association was not seen among women 

‘When [men] age, they lose their ability to stimulate T cells,’ Iwasaki told The Times.

‘If you look at the ones that really failed to make T cells, they were the ones who did worse with disease. [However] women who are older – even very old, like 90 years old – these women are still making [a] pretty good, decent immune response.’       

The study does not help explain why these differences exist between the sexes, but it does offer some clues.

In addition, the researchers say different types of vaccines and therapies may be needed for males and females.

‘Collectively, these data suggest that vaccines and therapies to elevate T cell immune response to SARS-CoV-2 might be warranted for male patients, while female patients might benefit from therapies that dampen innate immune activation early during disease,’ the authors wrote. 

‘Immune landscape in COVID-19 patients is considerably different between the sexes, and these differences may underlie heightened disease susceptibility in men.’

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