Melamed Lab

How Does Gender Impact Long COVID?

Written by: Akshara Ramasamy
Edited by: Esther Melamed

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-acute sequelae of COVID-19 (PASC), refers to a wide range of new or worsening health problems that patients may encounter after being infected with SARS-CoV-2 for more than four weeks.1,2

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.2,3 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.4 The majority of evidence for long COVID is limited, with very few studies focusing on the syndrome from a sex and gender perspective. 

Current evidence suggests that COVID-19 may trigger an autoimmune reaction in some people, which might explain why the syndrome tends to be more frequent in women (i.e. as women are more likely to develop autoimmune diseases).5 According to a study by women’s health experts Dr. Sabra Klein and Dr. Katie Flanagan, women tend to have stronger immune systems than men and greater vaccine efficacy as a result.6 While a robust immune response may be helpful in the early stages of a COVID-19 infection, it may also make women more susceptible to long-term autoimmune problems (as autoimmunity is thought to arise due to a mistaken overzealous immune response against the body’s self proteins, leading to damage of different body systems).

Researchers are now looking into the role of estrogen in long COVID development as one possible factor that may explain differences in immunological responses between men and women. A study from King’s College in London reported that post-menopausal women between the ages of 50 and 60 with low levels of estrogen were found to be at the most risk for long-term COVID symptoms.7 This 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 may be one potential link that could explain the significant differences and immune mechanisms involved in long COVID in women and men.

Despite increased evidence of the harmful consequences of long COVID, women may also be hesitant to speak with their health care provider because they are afraid of being ignored or ostracized, as several women have reported in an article by NBC news.8 Throughout history, women have had their chronic pain dismissed by physicians who reject them as “hormonal,” “hysterical,” or “emotional.”8,9 As women are disproportionately affected by long COVID, the pandemic has highlighted the sex disparity in symptoms and the great need for physicians to take women’s symptoms seriously.

With the rise of the Omicron variant and cases spiking once more, 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. Yomogida K, Zhu S, Rubino F, Figueroa W, Balanji N, Holman E. Post-Acute Sequelae of SARS-CoV-2 Infection Among Adults Aged ≥18 Years — Long Beach, California, April 1–December 10, 2020. MMWR Morb Mortal Wkly Rep 2021;70:1274–1277. DOI: http://dx.doi.org/10.15585/mmwr.mm7037a2
  3. 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
  4. 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
  5. Autoimmune response found in many with COVID-19. (2021, September 27). National Institutes of Health (NIH). https://www.nih.gov/news-events/nih-research-matters/autoimmune-response-found-many-covid-19
  6. 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
  7. 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
  8. “Just anxiety”: These women’s coronavirus symptoms persist but doctors are dismissive. (n.d.). NBC News. Retrieved December 15, 2021, from https://www.nbcnews.com/news/us-news/these-women-s-coronavirus-symptoms-haven-t-gone-away-doctors-n1235091
  9. Gaslighting in women’s health: When doctors dismiss symptoms | Northwell Health. (n.d.). Retrieved December 15, 2021, from https://www.northwell.edu/katz-institute-for-womens-health/articles/gaslighting-in-womens-health

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