Friday, April 16, 2021

JULIAN WILLETT'S COLUMN

Does Being Male Increase the Risk of Dying From COVID-19?

Physician review of the evidence regarding the impact of sex on COVID-19 mortality.

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Several factors increase one’s risk of severe COVID-19. Sex has been identified as a factor linked to mortality, with more men dying of COVID-19 than women¹. This article presents the data about this phenomenon and speculates why this occurs. In this article, I use “men” and “women” to refer to individuals’ sex at birth versus gender identity, which can be fluid and incongruent with their sex.

Paper Quality Details

I am referencing a meta-analysis from the journal Nature¹. Meta-analyses are among the most robust forms of medical evidence. Articles from Nature are chosen as being particularly impactful and based on robust science. The authors went over scores of different reports reviewing the cases of 3,111,714 individuals (all sexes), which is a lot of data and makes their conclusions stronger¹. All the authors appear based in a single research institution network in London, UK¹. This can sometimes be limiting as more diverse collaboration comes with different perspectives to appreciate data. Given a large amount of data, this likely has less of an impact on this paper.

They studied infections from January 1, 2020, to June 1, 2020¹. While we are further into the pandemic, there has not appeared to be much shift in the epidemiological profile of COVID-19 infections, so this should be okay. They instituted several steps meant to limit bias¹. Their choice of statistical measures appears to be appropriate¹.

Paper Results

In line with other published studies, there was no evidence that COVID-19 affects one sex more than the other¹. Being of the male sex was associated with a 2.84x higher risk of being admitted to an ICU than female¹. This means that if we had ten people with COVID who we knew would require ICU care, around seven of them would be men. This number’s real implication is that men were approximately three times as likely to have more severe disease because that is typically why individuals are admitted to an ICU.

When the authors further studied the risk of dying from COVID-19, men were on average 1.39x more likely to die from the illness compared to women¹. So were we to look back at a group of around 250 people who died from this terrible virus, roughly 150 would have been men and 100 women.

So what is it about being of the male sex that causes an increased risk?

Men and women’s immune system varies where women tend to have more systems in place to protect against infection¹. Past publications have found that women tend to have more “adaptive” immune cells, critical in defence against viral infections, and produce a more robust immune response¹. They also make more of an important signalling molecule at the beginning of infections that is particularly important for protection against COVID-19¹. This molecule’s production is influenced by hormones that are more rampant in women, like estrogen, and by the number of X chromosomes¹. Testosterone appears to have a suppressive effect on the immune system, which is not ideal when dealing with a dangerous virus¹.

While these explanations could provide an apt answer for what has been observed, it is worth citing that they are speculative. There remains a limited amount of data regarding COVID-19, so it isn’t easy to provide definitive answers at this time.

Conclusion:

Based on a paper that studied over a million individuals, males are at a higher risk of severe disease and death from COVID-19. This is likely related to sex-based differences in the immune system.

References:

  1. https://www.nature.com/articles/s41467-020-19741-6

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JULIAN WILLETT, MD

Medika Columnist

M.D. trained in the US, now researching SARS-CoV-2 and COVID-19 in Canada for his Ph.D. After earning my Ph.D., I will be pursuing an Anatomic Pathology residency embracing my path towards being a physician-scientist. My academic interests are directed towards topics that provide the greatest net benefit for the greatest number of people. I love complicated, messy, and poorly understood topics.

I enjoy writing in my spare time, along with 3D printing and staying connected with my family. I have been a longstanding proponent for global health with projects ranging from supporting Doctors without Borders (MSF) to Syrian refugees (Syrian American Medical Society).

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