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Sex, gender and COVID-19

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Data collected from many countries around the world suggest that men and women are equally likely to acquire COVID-19, but men have a higher risk of severe illness and death. Both sex and gender could help to explain why.

A chart comparing cases by age and sex vs. deaths by age and sex in Denmark. In age groups younger than 60, there are more identified cases of females with the coronavirus than males, but from ages 60-90, there are more males identified with the virus. Across all agre groups with deaths, more males than females with the coronavirus have died, according to this data.

Looking at data for 18 different countries, the Global Health 50/50 project found similar numbers of COVID-19 cases in men and women, except in Pakistan where 72% of cases were male.[1] As Pakistan is unusual in this set of data, there are doubts about the accuracy of reporting COVID-19 in women. In general, the observation that COVID-19 is just as frequent in men and women around the world will need to be verified with further testing.

In all countries that report death rates by sex, men diagnosed with COVID-19 are more likely to die. The male/female ratio of deaths among confirmed cases ranges from 1.1 in Iran to 2.1 in Denmark (see chart above) and Greece. The ratio of male/female death rates tends to be higher in older people: it is consistently above 2 in people aged 60 years and over, and more than 3 among men and women aged 70–79 years in Italy.

These findings are not unexpected. The outcomes of illness were worse for men than women during previous coronavirus epidemics: men had worse outcomes of illness from severe acute respiratory syndrome (SARS),[2] and a higher risk of dying from Middle East respiratory syndrome (MERS).[3]

In the UK, men with COVID-19 are more likely to need intensive care and they are more likely to die. In the first week of April 2020, the UK Intensive Care and National Audit Research Centre (ICNARC) published a report on the first 2,249 patients admitted to intensive care in the UK with COVID-19. It showed that in the 775 patients with full data, men with COVID-19 were more likely to die than women (53.2% v. 37.5%) and were over-represented among those needing mechanical ventilation (73% v. 27%) and basic respiratory support (71% v. 29%). ICNARC were also able to compare COVID-19 admissions with their data on viral pneumonia admissions from 2017–2019. This showed that 70% of COVID-19 admissions were males versus 54% of those with pneumonias caused by other viruses.[4]

Sex and gender

Although sex and gender are often used interchangeably, they have separate meanings. Sex refers to the underlying biological profile of a person. It influences a range of bodily responses that are important in tackling infection or disease. Gender refers to the roles, behaviours, activities and attributes that any given society considers appropriate for men, women, and people with non-binary identities. Gender determines what is expected, valued or allowed in the behaviour of men and women.

Both sex and gender could have a role in explaining why men have worse outcomes of COVID-19 infection than women, but no conclusive studies have yet been carried out.

One biological theory centres on the genetic differences between men and women, particularly in regard to the immune system. The X chromosome is known to contain the largest number of immune-related genes in the whole genome.[5] With their XX chromosome, women have a double copy of key immune genes compared to the single copy in XY men. This boost extends to both the general reaction to infection (the innate response) and also to the more specific response to microbes including antibody formation (adaptive immunity).[6] Thus women’s immune systems are generally more responsive to infections. This might mean women are able to tackle the novel coronavirus more effectively but this has not yet been proven.

A theory related to gender concerns tobacco smoking. About 50% of men in China smoke, but because it is not considered acceptable for women to smoke, only 2% of them do so. Preliminary data suggest that smoking is associated with adverse outcomes of COVID-19: for instance, the combined results of five studies showed that smokers were 1.4 times more likely than non-smokers to have severe symptoms of COVID-19 and 2.4 times more likely to be admitted to an intensive care unit, need mechanical ventilation or die.[7]

Taken together, the observations that smoking is more frequent among men than women, and that smokers are at higher risk of severe COVID-19 than non-smokers, are suggestive but not decisive. The next step is to investigate whether men with severe symptoms of COVID-19 also tend to be smokers, as compared with men who are infected but have mild symptoms or no symptoms.

Tackling the COVID-19 epidemic requires surveillance, testing and medical data broken down by sex and examined in the context of gender. These data will reveal any differences between men and women in the frequency of infection and the outcomes of illness. Understanding why such differences exist needs research on the biology of the two sexes as well as the social conditions in which they live.

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References

  1. COVID-19 sex-disaggregated data tracker. Global Health 5050. 2020 Apr.

  2. Karlberg J, Chong DS, Lai WY. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? American Journal of Epidemiology. 2004 Feb;159(3):229-231. DOI: 10.1093/aje/kwh056.

  3. Chen X, Chughtai AA, Dyda A, MacIntyre CR. Comparative epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia and South Korea. Emerging Microbes & Infections. 2017 Jun;6(6):e51. DOI: 10.1038/emi.2017.40.

  4. Report on 2249 patients critically ill with COVID-19. ICNARC. 2020 Apr.

  5. Bianchi I, Lleo A, Gershwin ME, Invernizzi P. The X chromosome and immune associated genes. Journal of Autoimmunity. 2012 May;38(2-3):J187-92. DOI: 10.1016/j.jaut.2011.11.012.

  6. Klein SL, Flanagan KL. Sex differences in immune responses. Nature Reviews Immunology. 2016 Oct;16(10):626-638. DOI: 10.1038/nri.2016.90.

  7. Vardavas CI, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tobacco Induced Diseases. 2020 ;18:20. DOI: 10.18332/tid/119324.

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