When it Comes to Coronavirus, Men are More Vulnerable

Sex differences in immune function appear to start right out of the womb, says an observer.

The details of the 99 coronavirus patients admitted to a Wuhan hospital were written up, as protocol demands, without fanfare.

“The average age of the patients was 55.5 years, including 67 men and 32 women,” said a Lancet paper published last month, which reported 11 deaths.

It is an eye-catching discrepancy. A picture is emerging of COVID19 as a novel pathogen that disproportionately affects older men, particularly those with existing illnesses such as heart disease and diabetes.

A similar pattern can be found in the statistics on SARS, which caused about 780 deaths nearly two decades ago. Some scientists are now convinced that these sex differences in clinical data reflect a genuine male vulnerability to coronaviruses, rather than a bias in exposure.

The observations add to growing evidence that, immunologically speaking, men are the weaker sex.

GENDER MATTERS

The new coronavirus is most often compared with SARS and Middle East respiratory syndrome (MERS), which originated on the Arabian peninsula in 2012.

SARS had an overall death rate of about 10 per cent, while MERS killed about a third of those infected. The figure for COVID19 seems to be about 3 to 4 per cent (that might fall as milder cases turn up).

Drilling down into the data, though, reveals that gender matters. One analysis of about 1800 SARS patients showed a death rate for men of 22 per cent, compared with 13 per cent for women.

A 2019 study of 229 MERS patients showed it killed 32 per cent of men compared with 26 per cent of women.

Possible reasons for disparities include smoking, variation in hospital treatment, and gender-linked immune response. That last possibility preoccupies Stanley Perlman, an immunologist at the University of Iowa, who has studied how SARS progresses in male and female mice. Middle-aged male mice fared particularly poorly.

The sex differences, he said, “seem to be consistent across coronaviruses. The effects are greater in mice than humans, I think, but there is always a male gender predominance.” He and colleagues suggest hormones – specifically oestrogen – might be key. And the size of the Wuhan outbreak, he suggests, could allow oestrogen’s role in disease defence to be teased out.

Some scientists are now convinced that these sex differences in clinical data reflect a genuine male vulnerability to coronaviruses, rather than a bias in exposure.

OUT OF THE WOMB

Sex differences in immune function appear to start right out of the womb. Baby girls are more likely to reach their first birthday than male newborns, according to the World Health Organisation.

Globally, women outlive men by an average of six to eight years. The WHO credits female longevity to an “inherent biological advantage”, as well as to healthier behaviour. Females are also more prone to autoimmune diseases, such as lupus, in which the body attacks itself.

This might be because women carry two X chromosomes (the X chromosome contains immunity-related genes, among others).

From an evolutionary point of view, an easily triggered immune response might be connected to childbearing; one theory is that while some parts of the female immune system are dialled down to avoid rejecting the foetus, other parts step up to compensate.

Given that modern women spend less time pregnant than their forebears did, this selectively exaggerated response might explain the high female levels of autoimmune diseases. That same overactive response might mean women clear the new coronavirus more quickly than men.

There is no upside to the current outbreak; a new chain of transmission has begun in Europe after a suspected “superspreader” travelled from a Singapore conference to a French ski resort, infecting others.

Still, rapidly growing patient numbers might yet reveal the secrets of female resistance.