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Why are women more susceptible to long COVID?

Long COVID has negatively impacted over 100 million people worldwide with residual symptoms that could persist many months or potentially a lifetime after resolution of the acute infection. After a year of devastating losses from COVID-19 infection, the beginning of 2021 offered hope with vaccine distribution. However, with progression of the pandemic into 2022, discussions surrounding the concept of long COVID emerged. Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as long COVID, post-COVID syndrome, and long-haul COVID, refers to the range of new, reemerging or persistent health issues patients endure after being infected with SARS-CoV-2 for four or more weeks. SARS-CoV-2 is a novel coronavirus that causes the infectious respiratory illness COVID-19. Symptoms of long COVID include shortness of breath, chest pain, brain fog, fatigue, myalgias, and gastrointestinal issues. While research is limited regarding this condition, a systematic review revealed that over half of individuals with SARS-CoV-2 infection experience long COVID for up to six months. 

The patient population with long COVID is predominantly women. Women are four times more susceptible to long COVID than men. This is not the first time we have observed a gender bias associated with COVID. Gender differences have been evident since the pandemic’s birth, as women are more likely to be infected with COVID, whereas men exhibit higher mortality rates with acute infection. The National Academy of Sciences defines sex as “being male or female, according to reproductive organs and chromosomes” and gender as “one’s sense of self as male or female in society.” 

Women and girls may be more susceptible to long COVID due to their stronger immune responses. Women have been shown to have heightened IgG antibody production, which is protective in the early phase of COVID-19, but can prolong inflammation if persistently elevated. Studies have also found that inflammatory marker IL-6 is elevated months after COVID-19 infection, especially in women. Immune T cells are more active in women than in men. Women have two copies of the X chromosome, which contains many genes coding for the immune system, whereas men have only one. Also, women of reproductive age have stronger immune systems because they have adapted to support pregnancy. Ultimately, all of these factors contribute to a hyperactive and prolonged inflammatory reaction in women that leads to the persistent fatigue, myalgias, cognitive changes and other symptoms that characterize long COVID.

This overactive immune response predisposes women to autoimmune conditions, in which the immune system produces autoantibodies that mistakenly attack one’s own tissues. There is a connection between autoimmunity and long COVID. Studies have detected higher autoantibody levels in COVID-19 patients that can persist for months, which can perpetuate inflammation and disease symptoms. It is suspected that this autoimmune response triggered by SARS-CoV-2 infection is more common in women.

Notably, women may face persistent complications in cardiovascular and pulmonary function due to long COVID. Women are shown to have slower reduction in heart rate following physical activity and decreased total lung capacity. These impairments were linked to decreased exercise tolerance and overall fatigue. The long-term symptoms of COVID-19 also impede women’s ability to work. Women already face a high percentage of job loss in society, but now many women have reported difficulty entering the workforce due to brain fog, pain, and chronic exhaustion from long COVID. There is a fear of unemployment as more days are taken off to recover from symptoms. This further exacerbates COVID-19’s disproportionate impact on women even beyond the health sphere.

In addition to multiple physical symptoms, women also experience psychological manifestations of long COVID. Depression, anxiety, memory issues, and sleep disturbances are common psychological consequences of long COVID. A survey reported an increase in depression during the pandemic among 83 percent of working women compared to 36 percent of working men. Financial stressors during the pandemic significantly impact women and compound mental health concerns.

Reporting bias and the dismissal of symptoms are contributing to the gender disparity in patients with long COVID. In general, women are thought to be more aware of the health and distress of their body. As a result of these assumptions about women, it has been found that their long COVID symptoms are often being dismissed as psychological in origin. There is limited medical research focused on conditions that mainly affect women because women’s symptoms tend to be attributed to emotions rather than actual medical conditions. 

Furthermore, reporting bias may be distorting long COVID data because more women than men tend to report symptoms. In general, women are more likely to seek out medical testing and care. It also tends to be more socially acceptable for women to discuss and report symptoms of fatigue, anxiety, pain, and distress. As a result, data that reflects higher rates of long COVID in women than in men could be a misrepresentation due to gender differences in reporting.

The COVID-19 pandemic has persisted beyond the two-year mark. While vaccines have protected countless individuals from severe illness and death, the virus continues to mutate into new variants and symptoms remain. Although the pandemic appears to be slowing down and individuals are trying to resume their pre-pandemic lives, it is important that we do not overlook certain populations that are disproportionately affected by long COVID. Long COVID has proven to be more prevalent and detrimental in women compared to men. The symptoms of long COVID have negatively impacted women’s ability to work, exercise, and perform other daily tasks. Moreover, these prolonged symptoms are often being dismissed as psychological in women, and there may be reporting bias as women are more likely to report symptoms. As a result, we believe that long COVID must be examined with a gender and sex lens in order to address the existing gender split in health implications of this syndrome. There needs to be increased recognition and research on patient experiences with long COVID and how they differ among women versus men. On a federal level, the government could implement initiatives, such as COVID awareness programs and long-term clinics, to inform and support the general population and health professionals. This will hopefully lead to an improved understanding of long COVID, which will ultimately develop into solutions. This includes implementation of preventive and therapeutic measures that will address long COVID and lessen the gender and sex disparities that commonly target women. Until then, long COVID and its gender bias are here to stay.

Lauren D’Annibale, BA, Danielle D’Annibale, MD, Akshara Ramasamy