Covid19

It gives me great pleasure to author another article for Bham Pharma Ltd as part of their Women’s Health online blog series. We seek to write about important and contemporary issues that affect the health of women across the globe to consider optimal health service delivery. For this reason, I am going to discuss the post-COVID-19 condition, otherwise known as ‘long COVID’, and its complex influence on the health of women. Specifically, I am going to attempt to answer the following question: does the post-COVID-19 condition affect more women than men? 

What is the post-COVID-19 condition?  

Throughout the development of the COVID-19 pandemic, it became apparent that a proportion of those infected with the SARS-CoV-2 virus experience complex and long-term health issues well after the acute infection phase of the disease. As the virus adapted, so too did the terminology for this long-term condition, with names including long COVID, long-haul COVID, post-COVID-19 syndrome, post-acute sequelae of COVID-19 (PASC), and chronic COVID syndrome (CCS). Due to the absence of a globally standardised clinical case definition for this condition, the World Health Organisation (WHO) conducted a clinical case definition working group meeting in October 2021. They conducted a two-round Delphi exercise, followed by an iterative consensus process with an assortment of stakeholders which included patients, patient researchers, external experts, and WHO staff. An 88-word WHO definition for the post-COVID-19 condition was created following the completion of the workshop: “Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms may be new-onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time” (1). The post-COVID-19 condition evidently causes a range of complex and debilitating symptoms which can vary over time; however, does it affect more women than men?

Emerging evidence indicates that the post-COVID-19 condition does affect more women than men 

Evidence suggests that women, especially those within the 40 – 60 age bracket, have a higher risk of experiencing a range of debilitating and ongoing post-COVID-19 symptoms compared to men. More reported symptoms can include fatigue, breathlessness, muscle pain, anxiety, depression, and “brain fog” after hospital treatment for COVID-19 (2). Additionally, women are significantly more likely than men to report, weakness, thoracic pain, palpitations, and sleep disturbances, but not muscle aches and cough (Pelà et al: 2022). Women are also statistically more likely to experience persistent symptoms such as shortness of breath, fatigue, chest pain, and palpitations (3). Using multivariate regression analysis, Pelà et al., were able to demonstrate that biological sex was a powerful determinant of long-term post-COVID-19 symptoms (1). Sex appears to be a critical factor in determining the persistence of shortness of breath, fatigue, chest pain, and palpitations in women who contracted the SARS-CoV-2 virus during the pandemic (3). 

Additional symptoms that were more frequently reported by female patients included: diarrhoea, partial or full loss of smell, chest pain, development of a taste disorder, weakness, palpitations, and muscle aches (3). Problematically, the range of symptoms that are caused by the post-COVID-19 condition can undermine normal day-to-day functioning which, in turn, can have a profound impact on individual mental health and wellbeing. For this reason, it is essential that healthcare professionals are informed about how the post-COVID-19 condition influences the individual quality of life status and that women are appropriately triaged for the services they need without delay.

What is causing women to experience more post-COVID-19 conditions compared with men?

At the time of writing, there is not a definitive answer to the question above. However, it is speculated that sex-based differences in the human immune response may be accountable for the higher prevalence of post-COVID-19 condition symptoms in women (Torjesen: 2021). Professor Tim Spector, based at King’s College London, notes that gender differences, in the way the human immune system responds to coronavirus, could account for the variance of post-COVID-19 symptoms between women and men (4). Naturally, this autoimmune-based hypothesis requires further research before any definitive statements can be posited in relation to the human autoimmune response and the more frequent expression of post-COVID-19 condition symptoms in women compared to men. An additional hypothesis is advanced by Pelà et al., who note that the medical literature suggests that women report symptoms affecting the body more frequently than men in both medical and community settings (3). It is asserted that physiological factors, sex hormone profiles, and differences in the functioning of the innate and adaptive immune systems may be related to the experience of pain (3). Obviously, all the hypotheses outlined above require further empirical investigation before any causal statements can be posited with any degree of confidence.

Time to keep researching to inform clinical action

Evidence indicates that women do experience the post-COVID-19 condition more than men. The symptoms of the post-COVID-19 condition are challenging, debilitating, and clinically complex. Given the range of long-term health issues caused by the SARS-CoV-2 virus, there is a clear need for urgent and robust research to help understand the epidemiological basis and the underlying biological mechanism for the sex difference in patients living with the post-COVID-19 condition (5). Significantly more research is needed to better understand the underlying determinants of the post-COVID-19 condition and why it appears to disproportionately affect women more than men. 

Importantly, there is a need for a sex- and gender-informed clinical approach in the treatment of this disease (3). Also, substantially more longitudinal studies are needed to fully understand the sex-related pathophysiology of the symptoms and the effects of the pharmacological treatment related to the post-COVID-19 condition. Future studies will be crucially important in understanding the natural trajectory of the post-COVID-19 condition, implementing targeted treatment strategies, and in securing equitable outcomes for females and males alike (3). Finally, it is essential that future studies, and the data that emerge from them, are used judiciously by healthcare providers to inform clinical decision-making and the management of the post-COVID-19 condition and its spectrum of symptoms.

References

  1. World Health Organisation (2021) A clinical case definition of post COVID-19 condition by a Delphi consensus. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1
  2. Torjesen, I. (2021) Covid-19: Middle-aged women face greater risk of debilitating long-term symptoms, BMJ, Vol. 372, No. 829. Available at: https://www.bmj.com/content/372/bmj.n829
  3. Pelà, G.,  Goldoni, M.,  Solinas, E., Cavalli, C., Tagliaferri, S., Ranzieri, S., Frizzelli, A., Marchi, L., Mori, P.A., Maria, M., Aiello, M., Corradi, M., Chetta, A. (2022) Sex-Related Differences in Long-COVID-19 Syndrome, Journal of Women’s Health, Vol. 31, No. 5 Available at: https://pubmed.ncbi.nlm.nih.gov/35333613/
  4. The Guardian (2020) Women aged 50-60 at greatest risk of ‘long Covid’, experts suggest. Available at: https://www.theguardian.com/world/2020/oct/21/women-aged-50-60-at-greatest-risk-of-long-covid-experts-suggest
  5. Stewart, S., Newson, L., Briggs, T.A., Grammatopoulos, D., Young, L., Gill, P. (2021) Long COVID risk – a signal to address sex hormones and women’s health, The Lancet, Vol. 11, No. 100242. Available at: https://www.thelancet.com/action/showPdf?pii=S2666-7762%2821%2900228-3
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