Already a few months after the first cases of Long COVID came up, it became apparent that women were more frequently affected than men. In the meantime, several studies have confirmed that the female gender is one of the most important risk factors for Long COVID. The exact numbers of how much higher the risk is for women to develop Long COVID differ depending on the study population. A large study in Spain and a meta-analysis of 16 publications on this topic reported a risk ratio of about 1.5, meaning that women have a 1.5-fold higher risk of developing Long COVID.
Many middle-aged women are affected
As early as June 2020, researchers in France observed that women – essentially women around 40 years of age without relevant medical conditions – had an increased risk to develop LC compared to men in general and women in other age categories.. In 2021, long-term follow-up of COVID-19-infected individuals in the US, the UK, Russia, and Bangladesh confirmed that young to middle-aged women are disproportionately affected.
Sudden difficulty concentrating and "brain fog": this is also one of the symptoms of Long COVID. Women suffer from it more often. (Symbol image: Adobe Stock)
A British study shows that women under the age of 50 reported to be five times less likely to feel recovered after COVID-19 infection, twice as likely to report fatigue, seven times more likely to suffer from shortness of breath, and more likely to be physically impaired than men of the same age. Another British study confirmed that women recovered less quickly than men after hospitalization.
Less acute, more protracted
Study author Chris Brightling suspects that gender differences in immune response are responsible for women being more likely to suffer from longer-lasting inflammatory responses and Long COVID symptoms. Men, on the other hand, are more likely to have a more severe or even fatal acute course but are less likely to suffer long-term sequelae. A study presented in May 2023 at the annual international conference of the American Thoracic Society also confirmed that women were significantly more likely to be affected by long-term constraints than men. It did not appear to have a noticeable effect on recovery whether the acute infection was severe or not.
The hypothesis: differences in genes and hormones could be responsible for the higher risk for females.
Autoimmune diseases are four times more common in women than in men. This could be related to the fact that the immune response in women is stronger than in men because of both genes and hormones. Many genes that regulate the immune system are located on the X chromosome. The fact that women have two X chromosomes results in a wider range of defense mechanisms. In autoimmune reactions, these mechanisms can be directed against the body's own proteins.
Fewer differences after menopause
Women also produce more estrogen, which can increase inflammation, and higher levels of a protein, which can lead to an overreaction of the immune system. Interestingly, the risk for Long COVID equalizes between men and women after age 60. This is another indication that hormones play a role, as estrogen levels drop in women after menopause.
It's double-edged: what protects women from a severe course seems to favor long-term consequences.
In the US, immunologist Akiko Iwasaki has spent a lot of time deciphering the differences between men's and women's responses to SARS-CoV-2. One of her initial findings was that T cells – immune cells that seek out and destroy infected cells – are much more active in the early stages of infection in women than in men. The stronger T-cell response saves women's lives. However, it can also cause the immune system to attack itself.
In the process, fragments of the virus can become lodged in the tissue. It is possible that these fragments can trigger chronic inflammation throughout the body and thus a long-lasting syndrome, according to researcher Noah Greenspan, who has studied Long COVID in students in the United States.
That men are more likely to develop severe symptoms, be hospitalized and die despite the same risk of infection was shown by US researchers as early as late 2020. They also explained the female advantage in acute COVID-19 disease by sex differences in the immune system.
Men are at higher risk for a severe course of COVID-19, but they are less likely to suffer from long-term consequences. (Symbol image: Adobe Stock)
Evidence of sex differences is already known from studies of chronic fatigue, which is four times more common in women. Females have been found to suffer more often from autoimmune-related complaints, ranging from new allergies to muscle stiffness and joint pain – and usually have a similar symptom profile to Long COVID. Conclusively, there may be a general pattern emerging here: Women are better protected from severe infections due to their immune system but have a higher risk of developing prolonged symptoms.