Since the beginning of the COVID-19 pandemic, acute cases of the disease–particularly those requiring hospitalization–predominantly affected men over the age of 50. In contrast, the majority of long COVID sufferers have been young to middle-aged women. Some experts are asking why this might be the case.

A Long-COVID Patient Profile Emerges

Between May and July 2020, a Paris hospital reported that women experiencing long-term effects of COVID were about 40 years old and that they outnumbered men by a ratio of four to one. Over the last 12 months, similar reports have come from all around the globe, from Bangladesh and Russia to the UK and the U.S. 

Dr. Sarah Jolley of the UCHealth post-COVID care clinic in Colorado said that about 60% of her patients have been women. Dr. Petter Brodin, who leads the long COVID branch of the COVID Human Genetic Effort in Sweden, suspects that the overall proportion of female long COVID patients may be between 70 and 80%.

The phenomenon is not restricted to long COVID. “This pattern has been seen in other post-infectious syndromes,” said Dr. Melissa Heightman, who runs the UCLH post-COVID care clinic in north London. She pointed out that women are up to four times more likely to develop chronic fatigue syndrome (believed to have infectious origins) and are significantly more likely to suffer chronic symptoms from Lyme disease.  

Gender Bias

Unfortunately, there have been few attempts to explore why this is the case. Since these conditions predominantly affect women, they have often been dismissed as being psychological in origin. “In general, there’s not as much research money and attention on conditions that primarily affect women,” said Julie Nusbaum, an assistant professor at NYU Long Island School of Medicine. 

There have also been myriad reports of female patients having their persistent symptoms dismissed by medical professionals communities. Dr. Janet Scott, an infectious diseases specialist at the University of Glasgow, says that she thinks “it plays into the narrative of, ‘Don’t worry about long COVID, it’s just a bunch of hysterical, middle-aged women.’”

Despite those who minimize the problem, Scott and others are investigating the possible reasons for the unequal burden by sex. Understanding them may be critical to unraveling not only long COVID but also other illnesses for which infection is a catalyst. There are several hypotheses. 

Pregnancy 

Professor Akiko Iwasaki, an immunologist at the Yale School of Medicine, has been studying the differences between men’s and women’s responses to the SARS-CoV-2 coronavirus. She found that T cells (that seek out and kill viruses in the body) are far more active in women than in men in early-stage infections. “Women have two copies of the X chromosome,” said Iwasaki. “And many of the genes that code for various parts of the immune system are located on that chromosome.”

Women of reproductive age are thought to have more evolved–and reactive– immune systems, to support the greater need for protection during pregnancy. It’s thought that this may help explain the lower death rate from acute COVID among women. 

Since scientists also suspect that remnants of the virus linger in diverse pockets of the body, it’s possible that this, coupled with a heightened immune system response, could set off surges of chronic inflammation. According to Iwasaki, Sars-CoV-2 remnants have been found in almost every kind of tissue in the body, from the kidneys to the brain, hence the diversity of symptoms such as brain fog, pain, and fatigue.

Comparable results have been found in Lyme disease studies. Research shows that women have more severe responses to Borrelia burgdorferi, the bacterium that causes Lyme disease, developing much higher levels of inflammatory proteins than men do.

Autoimmune Diseases

That would only be part of the puzzle, however. Scientists think that, at least in some cases, SARS-CoV-2 may spark an autoimmune disease in which autoantibodies attack the body’s own organs. In the last several months, several studies have identified elevated levels of more than 100 autoantibodies in COVID-19 patients. These autoantibodies have attacked a wide variety of tissues, including brain tissue and blood vessel linings.  

Similar events have been discovered in studies on chronic fatigue syndrome. Women are much more likely to experience autoimmune-related ailments, including many of those seen in long COVID: muscle stiffness, joint pain, new allergies, etc. Women make up 78% of all autoimmune cases in the U.S., and viruses have long been linked to the onset of autoimmune diseases. 

Why are women more prone to autoimmune problems? Three known reasons include:

• VGLL3, a protein-coding gene that women have much more of than men do and which can send their immune systems into overdrive
• The female sex hormone estrogen, which can increase inflammation 
• Men’s higher levels of testosterone, which suppress the generation of B cells (that produce autoantibodies)

Seeking Answers

Some scientists are focusing on long COVID as an estrogen-related autoimmune disease and are calling for more research to help formulate sex-specific treatments. Greater understanding of the virus’ sexual bias will hopefully also shed light on other inflammation- and autoimmune-based illnesses with higher prevalence in women than in men.

“I do think it’s possible that the attention now being placed on long COVID could help provide an insight into that,” said Nusbaum, “which would be a very welcome benefit.”

*Cox, D. (2021, June 13). Why Are Women More Prone to Long Covid? The Guardian. https://www.theguardian.com/society/2021/jun/13/why-are-women-more-prone-to-long-covid 

Much about the novel coronavirus, i.e., COVID-19, is still not fully understood. As research progresses and our knowledge of the virus increases, information can change rapidly. We strive to update all of our articles as quickly as possible, but there may occasionally be some lag between scientific developments and our revisions.