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Infectious Diseases

Updated 06 October 2020

More evidence shows why Covid mortality rate is higher in men

Two recent studies presented at the ESCMID Conference on Coronavirus Disease shows why men with Covid-19 have worse outcomes than women.

  • Recent research presented at an online conference offers more insight into why Covid-19 affects males more severely than females
  • The studies looked at inflammation, circulating proteins and immune system cells in both sexes
  • Further research is needed to understand exactly why these differences exist

Scientists have been trying to understand why Covid-19, the disease caused by SARS-CoV-2, affects men more severely than women.

Previous studies have found clues in the presence of antibodies, as well as the immune responses in the two sexes. And two recent studies offer further explanations.

Both published papers were presented at the ESCMID Conference on Coronavirus Disease (ECCVID), which took place online from 23–25 September, EurekAlert reports.

One is a German study that confirms that men have a higher risk of Covid-19 associated death compared with women, and researchers found that this is possibly related to higher levels of inflammation in men.

The second study by researchers from the Netherlands explains that Covid-19 mortality in men could be explained by differences in circulating proteins and immune system cells.

Men and inflammation: the link

The German study, led by Dr Frank Hanses from University Hospital Regensburg in Germany, and colleagues, showed that men have a 62% increased risk of Covid-19 associated death compared with women. This was after adjusting for various factors.

For their study, the team drew on data from the international multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) registry, established during the Covid-19 pandemic.

They then assessed 3 129 adult patients with Covid-19 who were enrolled between March and July 2020, and described clinical manifestation of Covid-19 in four phases: 

  • Uncomplicated (asymptomatic/mild symptoms)
  • Complicated (need for oxygen supplementation)
  • Critical (need for critical care) 
  • Recovery

The patients’ symptoms, vital signs, inflammatory markers and therapeutic interventions were also studied during all phases. The researchers noted that progression to a critical phase (ICU admission) was seen more often in men than in women (30.6% vs. 17.2%). Mean hospital length of stay was also longer in male patients (15.4 vs. 13.3 days).

Men also had significantly higher inflammatory markers across all phases of the disease, the researchers added, and further commented:

“Men are more likely to progress to critical phases of Covid-19. Men have higher death rates as well as more frequent ICU admissions and longer hospital stays, that are all associated with higher inflammatory parameters during all phases of Covid-19.

“In our cohort, this effect was not explained by differences in comorbidities, age or BMI between male and female patients."

The team concluded that further studies on what exactly makes men more vulnerable to Covid-19 are needed, as scientists don’t yet know which biological, or possibly social factors, lead to these marked differences.

Covid-19, circulating proteins and immune system cells

The second study by Gizem Kilic from Radboud University Medical Center in Nijmegen, Netherlands, and colleagues, suggests that the higher risk of poor Covid-19 outcomes in men could be explained by differences in circulating proteins and immune system cells compared with women.

In this study, the researchers assessed the levels of circulating inflammatory proteins and whole blood cell populations related to Covid-19 infection severity in two healthy Western European cohorts, and investigated whether these immune parameters differ between males and females.

Senior co-author, Professor Mihai Netea, from Radboud University Medical Center explained that they identified several circulating inflammatory proteins and cell populations, which might be behind the higher susceptibility of males to severe Covid-19 disease.

The team also found that certain white blood cells in the immune system, reported to decrease with Covid-19 severity, were also lower in healthy males.

In addition to the above, the researchers found that molecules involved in inflammation and that stimulate immune and epithelial cells were high in healthy males, and also in patients in ICU, indicating that immune mediators contributing to severe Covid-19 infection are already intrinsically higher in males.

"Sex is one of the major factors which influence our immune system response. Our results suggest that differences between the sexes in the baseline characteristics of the immune system such as circulating proteins and immune cell populations might explain the predisposition of males over females to develop severe Covid-19 infection," the researchers concluded.

READ | The Covid-19 virus is deadliest if you are older and male – scientists looked at the risks

READ | Why does Covid-19 hit men harder than women? The immune system reveals some clues

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