MEN have died of Covid-19 at about twice the rate of women, according to data from the Office of National Statistics.
Similar patterns were seen during earlier outbreaks of SARS, a related but less deadly coronavirus infection that first appeared in China in 2002; and of MERS, which first appeared in Saudi Arabia in 2012.
At first, scientists assumed the differences were due to different smoking rates between the sexes. Now, however, there is growing evidence that women have much more effective immune systems. They are generally more resistant to infection caused by bacteria and viruses, and seem to be able to harness a better response when they are attacked by disease-causing agents such as bacterial tuberculosis, as well as influenza-type viruses such as Covid-19.
They also respond better to vaccines, making many more antibodies against whatever infection the vaccine is targeting – particularly flu, which is related to Covid-19.
The immune system network is influenced by sex hormones, which also seem to provide better immunity in women. The decline in hormone levels in old age might be one of the reasons the immune system in both women and men becomes less efficient.
Stress and sleep deprivation also damage immunity, as does ‘overnutrition’. People who are obese or have conditions such as type 2 diabetes have impaired resistance to infection, which helps explain why the majority of Covid-19 deaths have involved people who are overweight.
The downside of this active female immune system is that it is prone to go into accidental overdrive, leading to auto-immune diseases such as rheumatoid arthritis, which is far more common in women.
A growing understanding of genetics has revealed what might be going on, with large concentrations of genes controlling immunity and regulation of the body’s defence systems on the X chromosome.
Women inherit two X chromosomes, one from each parent; men inherit a Y chromosome conferring male characteristics from their father, and an X chromosome, which sits alongside it, from their mother.
Geneticists had believed that only one of the X chromosomes was doing very much in women, but now they have discovered that the second one provides a comprehensive back-up service when required.
It means if women have a defective gene on one X chromosome, it could be cancelled out by the work of a better quality gene on the other. This may explain why women generally outlive men. While many doctors have claimed that fewer women than men are contracting Covid-19 in the first place, Professor Priya Duggal, director of the genetic epidemiology programme at Johns Hopkins University in Maryland, US, says infection rates are the same.
"We don’t see a difference in infection, we see a difference in survival," she says. "The people dying from it tend to be adult males with comorbidities [other underlying illnesses], but we don’t see as many deaths in women with the same comorbidities."
She believes the way forward lies in observing the activity of different genes in men and women at different stages of the disease, in order to understand what genes are active in women but not in men.
Meanwhile, work at the University of Michigan has focused on a specific type of immune cell called mast cells. The team has found that while such cells from men and women have the same genes (with the exception of the sex chromosome gene), their levels of activity vary dramatically.
There are 4,000 genes that are more active in female mast cells than in male ones, undoubtedly contributing to the better immune response.
The goal is to try to identify what these efficient elements of the female immune system might be, in the hope that the substances made by these genes might be developed into medicines to help fight off life-threatening infection.
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