Severe COVID much more common in males, research shows

Doug Hendrie

11/12/2020 1:29:29 PM

Men are almost three times more likely to develop severe COVID-19 and enter intensive care, according to a new meta-analysis.

Man with COVID being treated in ICU.
New research confirms that COVID poses a higher risk to men.

The Nature Communications analysis of 92 studies covering more than three million patients found that while males and females seemed equally susceptible to infection, men were 2.84 times more likely to be admitted to intensive care and 1.39 times more likely to die.
Led by South African researcher Dr Kate Webb, the research validates country-level studies finding the same phenomenon, and may inform public health authorities as they debate in what order groups in society should be immunised.
‘[T]he ubiquitous nature of the sex-bias in these data argues for a true biological difference in the response to SARS-CoV-2 between sexes,’ the paper states.
The findings are in line with heightened male susceptibility to infectious disease broadly, with a higher burden of bacterial, viral, fungal and parasitic infections in males.
‘Previous coronavirus outbreaks have demonstrated the same sex bias,’ the researchers state, noting that the 2003 epidemic of the related coronavirus SARS-CoV-1 had a similar age-adjusted relative mortality risk ratio of 1.62 in Hong Kong and even higher in Singapore.
Reasons for this discrepancy may include different immune responses between the sexes, according to the researchers, alongside other biological factors and comorbidities. 
There are also differences in how males and females express the key angiotensin converting enzyme-2 (ACE-2) receptors that SARS-CoV-2 latch onto to gain access to human cells.
‘Sex differences in both the innate and adaptive immune system have been previously reported and may account for the female advantage in COVID-19,’ the research states. ‘Within the adaptive immune system, females have higher numbers of CD4+ T cells, more robust CD8+ T cell cytotoxic activity, and increased B-cell production of immunoglobulin compared to males.
‘Women report more severe local and systemic side effects, and produce higher antibody titres in response to the trivalent inactivated seasonal influenza vaccination (TIV)100, as well as to most other pathogen vaccines.
‘These findings imply that females have an increased capacity to mount humoral immune responses compared to males, and together with the data from this meta-analysis, may have important implications for the development of vaccination strategies for COVID-19.’
What is less clear is the extent to which sex-based behavioural and socio-cultural differences influence COVID severity. For instance, while men are more likely to smoke, the habit has not emerged as a clear risk factor for severe disease, the researchers state.
Men are also less likely to wash their hands with soap, and in some cultures, may be more likely to leave the house and socialise in crowded areas.
However, given there are no sex-based differences in infection rates, these different behaviours are unlikely to influence the differences in disease severity, the researchers state.
Two professors at the Yale School of Medicine noted in June that women tend to have a ‘more robust immune response to disease-causing viruses and bacteria,’ with potential links to X chromosomes improving the expression of key immune functions, as well as the possibility that oestrogen and progesterone can help promote immune response and reduce inflammation.
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