The amount of COVID detected in Perth’s wastewater has reached its highest level in 12 months.
This means the traditional family jibes about men who take to their beds complaining of debilitating symptoms while similarly affected women soldier on with work, chores and childcare will probably reach their highest level too.
The term “man flu” even has its own entry in the Oxford English Dictionary, as “a cold or similar minor illness that somebody, usually a man, catches and treats as if it were flu or something more serious”.
However, behind all the gendered joshing there is a serious side to man flu, which could also explain why cancer rates are significantly higher in males while painful autoimmune diseases — such as rheumatoid arthritis — are more common in females.
It may even explain why the Covid-19 pandemic killed many more men than women. Data from the Office for National Statistics show that in the opening months of the pandemic in 2020, men in England and Wales were dying of coronavirus at twice the rate of women.
For decades, scientists have debated whether man flu is real or not.
In a new book, How To Stay Healthy, nutritionist Jenna Hope argues “the evidence shows the female immune system is stronger than the male immune system”, and suggests it’s down to hormones — the female sex hormones progesterone and oestrogen tend to support the immune system, while the male hormone testosterone can suppress immunity.
In fact, the role of oestrogen in female immunity was highlighted by immunologists at Johns Hopkins University in Baltimore, Maryland, in 2016.
They infected cells from men’s and women’s nose linings with a common flu virus (seasonal influenza A), before adding the most common form of oestrogen in women, called oestradiol, to all the cell cultures.
In the women’s cell cultures, the oestrogen resulted in a significant drop in levels of the flu virus. But the virus levels in the men’s cell cultures remained unchanged, reported the American Journal of Physiology-Lung Cellular and Molecular Physiology.
Both sexes produce oestradiol: men make a tiny amount in their testes (possibly to aid sperm production) while women release large amounts from their ovaries, mainly to build and maintain their reproductive system.
By contrast testosterone, the main male hormone, appears to suppress immune defences, probably because it drives activities, such as building muscles that demand energy.
For example, a study by immunologists at Stanford University in California, published in 2014, found that men with higher-than-average levels of testosterone had lower levels of antibody response when given jabs.
In evolutionary terms, researchers surmised, reduced immunity was less important for men than looking powerful and fathering quickly; males are more likely to die in fights or accidents before an infection kills them.
A study earlier this year found having a poor night’s sleep seriously diminished the amount of protection conferred by a vaccine the next day — but only in men.
The research, published in the journal Current Biology, analysed previous studies involving over 500 men and women and showed that men who slept for fewer than six hours the night before receiving a vaccination against flu or hepatitis had far fewer antibodies than those who slept for seven hours or more.
The net effect was to knock two months off the time a man was protected by the jab. Yet there was no such loss in women who had little sleep before a jab.
But why would women have stronger immune systems than men?
From an evolutionary perspective, having a strong immune system enables women to best protect the foetus from infections being passed from them to the baby in the womb, says Francisco Úbeda de Torres, a professor of mathematical biology who studies evolution and health at Royal Holloway, University of London. This process is called ’vertical transmission’.
As Professor Úbeda de Torres explains: ’When pregnant women contract infections from people around them, they can transmit them to their offspring in the womb through the placenta.
“Evolutionary pressures have meant women and their babies survive best if the mothers’ bodies mount a strong immune response to pathogens, to protect the offspring as effectively as possible.”
But women can sometimes pay a painful price for this ability to protect their unborn young in this way, he says.
“All the evidence indicates that this comes at a cost in terms of much higher incidence of autoimmune disease.”
Autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and psoriasis occur when the immune system overreacts and attacks healthy tissues.
Research suggests that around 80 per cent of patients with autoimmune diseases are women (but more on this later).
Men, meanwhile, can pay a heavy price for running weaker immune responses, adds Professor Úbeda de Torres — and this can go far beyond man flu.
“Men produce a weaker response and are at significantly higher risk of developing many cancers compared to women,” he says.
“This is because a weaker immune response means pathogens are able to infect men for longer — giving viruses or bacteria more time to tamper with the genetics of the cells they infect.
“One of the things these pathogens can do is make the infected cells proliferate.
“This helps infections to spread through men’s bodies, but it also increases the risk of cells rapidly replicating out of control and becoming cancer.”
That weaker response took a tragic toll on men during the Covid-19 pandemic, according to an analysis of data released by the King’s Fund last year. In 2019, life expectancy at birth in England stood at 79.9 years for men and 83.6 years for women — a difference of 3.7 years.
However, because COVID killed significantly more men than women, in 2020 and 2021 the gender gap widened to four years —with men’s life expectancy falling to 78.6 years compared to 82.6 years for women.
When it comes to mounting stronger immune responses to infections, emerging research suggests that women have another secret weapon, which is concealed in their chromosomes.
As Tim Vyse, a professor of molecular medicine at King’s College London, explains: “In terms of human chromosomes, women are XX and males are XY — but you only need one X chromosome to regulate the immune system. So when females are in the womb the influence of one of the Xs is largely shut down.”
However, this shutting down process is not as neat and tidy as previously thought, adds Professor Vyse. “Some of the influence of the extra suppressed chromosome still comes through — which we call ‘X evasion’.
“We think this X evasion may confer some evolutionary advantage with stronger immune defences but may also drive higher levels of autoimmune disease in women.” (In other words, their robust immune system can go into overdrive and more easily trigger an attack on their own tissues.)
A gene called UTX may play a key role: this gene is located on the X chromosome, so therefore women — with their two Xs — have one more copy of UTX than men.
In a 2023 study in the journal Nature Immunology, researchers at the University of California, Los Angeles found that the UTX gene — and the protein it effectively ’produces’ — are important for regulating the function of natural killer (NK) cells.
NK cells are part of our immune system — they kill cells infected by viruses and rogue cancer cells.
The study suggests that because females have double the UTX gene, they have more of the UTX protein in their natural killer cells — experiments the scientists performed indicated that a double dose of UTX boosts the NK cells’ anti-viral function — meaning women are better able than men to protect themselves against viruses.
Professor Vyse’s research has shown how this strengthened defence can be a double-edged sword.
“We have found that women with the autoimmune disorder lupus [a long-term condition that causes joint pain, skin rashes and tiredness] had better COVID-19 outcomes than women who did not have lupus. This suggests there’s a balance to be had between autoimmune disease risk and infection risk.”
Why could this be?
Professor Vyse has an evolution-based explanation: “It may be that biology wants females to survive infectious outbreaks more.
“You can lose 50 per cent of the males from a human population and it won’t really matter, the population will compensate and the population will survive.
“However, a human population would most likely be devastated if it loses 50 per cent of its fertile breeding females.”
But while men, in evolutionary terms at least, appear rather dispensable, studies show they are also less likely to take preventive care or seek care when ill.
So maybe it’s time the weaker sex looked after itself much more carefully.