Sex and Gender Differences in Long COVID

Among the several health impacts of the COVID-19 pandemic, a few medical challenges remain, including understanding the etiology of long COVID. Long COVID, also known as post-COVID syndrome, refers to a wide range of new, returning, or persistent health problems that patients may encounter after being infected with SARS-CoV-2 for more than four weeks [1].


As researchers strive to understand who is more susceptible for long COVID-19, data shows that women are more likely than males to develop it [2]. Gender differences have been apparent since the start of the pandemic, when men were found to have higher mortality rates but female infection rates supersede that of males [3]. The majority of evidence for long COVID is limited, with very few studies focusing on researching the syndrome from a sex and gender perspective.


In November, the faculty and students at the University of Texas at Austin gathered for a roundtable and discussed how a sex and gender-specific lens is needed in addressing the long-term consequences of COVID-19. Dr. Esther Melamed, an assistant professor of neurology at UT Austin’s Dell Medical School, explains that coronavirus may trigger an autoimmune reaction in some people. In other words, long COVID could be linked to immunological response, which might explain why the syndrome tends to be more frequent in women. According to a landmark study by women’s health experts Dr. Sabra Klein and Dr. Katie Flanagan, women typically have stronger immune systems than men and greater vaccine efficacy as a result [4]. While a robust immune response may be helpful in the early stages of the infection, it may also make women more susceptible to long-term autoimmune problems.


Moreover, Dr. Melamed and researchers across the world are looking into the role of oestrogen in long COVID development. A study from King's College in London reported that post-menopausal women between the ages of 50 and 60 with low levels of oestrogen were found to be at the most risk for long-term COVID symptoms [5]. The hormone interacts with the immune system in a variety of ways, including regulating the creation of immune cells and their response to infection. Consequently, sex hormones might explain the significant differences and immune mechanisms involved in long COVID.


As the discussion came to a close, participants highlighted how new and ongoing studies should account for and investigate sex and gender differences in the onset and course of long COVID. As the world prepares to enter the third year of the COVID-19 pandemic, identifying probable interactions of sex as a biological variable on this enigmatic syndrome is essential to revealing potential treatments.



References

  1. What doctors wish patients knew about long COVID. (n.d.). American Medical Association. Retrieved December 10, 2021, from https://www.ama-assn.org/delivering-care/public-health/what-doctors-wish-patients-knew-about-long-covid

  2. Sudre, C. H., Murray, B., Varsavsky, T., Graham, M. S., Penfold, R. S., Bowyer, R. C., Pujol, J. C., Klaser, K., Antonelli, M., Canas, L. S., Molteni, E., Modat, M., Jorge Cardoso, M., May, A., Ganesh, S., Davies, R., Nguyen, L. H., Drew, D. A., Astley, C. M., … Steves, C. J. (2021). Attributes and predictors of long COVID. Nature Medicine, 27(4), 626–631. https://doi.org/10.1038/s41591-021-01292-y

  3. Wehbe, Z., Hammoud, S. H., Yassine, H. M., Fardoun, M., El-Yazbi, A. F., & Eid, A. H. (2021). Molecular and biological mechanisms underlying gender differences in covid-19 severity and mortality. Frontiers in Immunology, 12, 1603. https://doi.org/10.3389/fimmu.2021.659339

  4. Klein, S. L., & Flanagan, K. L. (2016). Sex differences in immune responses. Nature Reviews Immunology, 16(10), 626–638. https://doi.org/10.1038/nri.2016.90

  5. Post-menopausal women at higher risk of developing severe COVID-19, study finds. (n.d.). Retrieved December 10, 2021, from https://www.kcl.ac.uk/news/post-menopausal-women-higher-risk-developing-severe-covid-19


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