Most day-to-day diseases don’t seem to care what sex you are: man or woman, those coughs, colds and stomach bugs latch on regardless.
But there’s clear evidence that COVID-19 is different. Across the world, scientists are reporting that men are much more likely to suffer severe symptoms from the illness, meaning more will succumb.
So what factors could be important? The most obvious are lifestyle-related: in the UK, according to the Office of National Statistics (ONS), more men (16.5 per cent) than women (13 per cent) still smoke. And if you’re a smoker, you’re already more likely to die from lung or heart disease, which would likely make recovery from COVID-19 more difficult as these are already on the ‘high risk’ categories.
Obesity has also been linked to how hard Covid-19 can hit, with France’s chief epidemiologist Professor Jean-François Delfraissy saying being overweight is a major risk factor for people infected with the novel coronavirus.
Drinking habits might matter too; alcohol is a causal factor in more than 60 medical conditions, including: mouth, throat, stomach, liver and breast cancers; high blood pressure, cirrhosis of the liver; and depression. And men drink at problematic levels more than women: In the UK for example, Public Health England figures state that of those seeking treatment for alcohol use, 60 per cent are men.
But could something deeper be going on at a cellular level? Nanotechnologist Dr Michelle Dickinson, creator of Nanogirl STEM Adventure subscriptions, says that while mechanisms that underlie differences between the sexes are complex and there are some behaviours seen more in men (such as smoking), how our bodies react to Covid-19 seems to revolve more around immunological, hormonal, and genetic factors.
“This is not the first time we have seen this gender difference,” says Dr Dickinson. “SARS, influenza, Ebola and HIV have all affected men differently to women.
“Research shows that women’s bodies are better at fighting off infection, thanks to hormones and the many immune function genes that sit on their two X chromosomes (men only have 1 X chromosome).”
This means women typically have stronger immune responses than men, except during pregnancy to help them avoid attacking their foetus. This is thought to be related to the female hormone oestrogen, which has been shown to bind to immune cells and activate disease-fighting molecules.
“When mice were infected with SARS,” explains Dr Dickinson, “male mice were more likely to die, until the researchers removed the ovaries (and therefore oestrogen) from the female mice, after which their death rates skyrocketed.”
University of New South Wales researcher Zoe Xirocostas has just published a hypothesis called the Unguarded X into why women live longer than men generally. She explains why having two matching X chromosomes (as in human females) is advantageous to longevity: “The hypothesis suggests that having a small Y chromosome (as in human males) means you would be more likely to express undesirable traits if there was something wrong with a gene on one of your X chromosomes.
“Whereas in females, having two X chromosomes means if something is wrong with a gene on one chromosome, you are likely to have a functioning version of that gene on your other X chromosome and essentially hide (or mask) any mistakes, and therefore not express the undesirable trait. These undesirable traits could be anything that is housed on the X chromosome.”
As an example, she says, a faulty gene might play a small role in immunity or respiratory function. As explained by the hypothesis, men would be more likely to express this faulty gene than women (because women have an extra X chromosome that would likely have a good copy of this gene) and therefore have the immune/respiratory system function in a way that is not ideal.
Normally, a small genetic error like this would go unnoticed as the body is still able to function normally, however, in the case of coronavirus, it could be a big factor affecting how you are able to fight the disease.
Xirocostas also points out that testosterone has been shown to act as an immunosuppressant, which could also play a role in men dying at higher rates than women for coronavirus.
Meanwhile oestrogen enhances immune defence and acts as an antioxidant, says a Danish analysis published in the journal PNAS in 2018, which looked into why women live longer than men even during epidemics.
The research team led by epidemiologist Prof Virginia Zarulli points out that many bacterial, viral, parasitic, and fungal infectious diseases are higher in men than in premenopausal women.
Plus, autoimmune diseases are more prevalent in women than in men, as is a stronger immune response to vaccinations, although the mechanisms through which sex hormones affect immune responses in humans have not been fully elucidated.
Could innate fitness also matter? Women process oxygen more quickly than men when they start to exercise, according to a 2017 study from the University of Waterloo. “We found that women’s muscles extract oxygen from the blood faster, which, scientifically speaking, indicates a superior aerobic system,” said Richard Hughson, a professor in the Faculty of Applied Health Sciences, and Schlegel Research Chair in Vascular Aging and Brain Health at Waterloo.
By processing oxygen faster, women are less likely to accumulate molecules linked with muscle fatigue, effort perception and poor athletic performance.
Is it also a question of exposure? More women seem to be contracting the virus in the first place with US data showing that while more men are dying of Covid-19, in most states, slightly more women are getting infected.
This could be due to the sex-based nature of health workforces – according to the UK’s NHS Digital, 77 per cent of the whole NHS workforce is female, with most in lower paid or junior roles.
Another factor where gender matters is a protein called ACE2. Dr Dickinson explains: “COVID-19 prefers to infect and latch on to cells that have this ACE2 protein on the outside. Recent (though not peer reviewed) research on COVID-19 infected patients in China showed higher circulating ACE2 levels in men than in women and in patients with diabetes or cardiovascular diseases.
“While there is still more research to be done, it does seem that females are designed to have a more robust immune response to COVID-19.”