Post-COVID-19 condition, or long COVID, is diagnosed when neurological, respiratory, or gastrointestinal symptoms develop or persist for 3 months or more after acute SARS-CoV-2 infection.
According to “Medical Xpress,” the likelihood of developing long COVID is three times higher in women than in men, but until now, the underlying biological mechanisms leading to this disparity have remained unknown.
Lead researcher Shoukhrat Mitalipov, professor of immunology at the Mike Petrik School of Dentistry, said: “We are focusing on a subset of patients with very severe symptoms, much like chronic fatigue syndrome.” He added: “They did not have these symptoms before COVID-19, and most of them had only mild symptoms, so they were not hospitalized.”
Ilahi’s team conducted blood and genetic tests on 78 patients with long COVID one year after their acute diagnosis, in addition to a control group of 62 individuals who did not develop long COVID after SARS-CoV-2 infection.
Through analysis of immune cells, biomarkers in the blood, and RNA sequencing, the researchers were able to identify a distinct immune signature in female patients compared to male patients.
The researchers found evidence of “leaky gut” in female patients, including elevated blood levels of intestinal fatty acid-binding protein, lipopolysaccharide, and soluble protein CD14 – all signs of intestinal inflammation that can then trigger further systemic inflammation once they reach the circulatory system.
Ilahi stated: “This suggests that perhaps in the early stage of the disease, when patients have an acute coronavirus infection, there is a tendency for the intestines of females to be more susceptible to the virus.”
The team also found a decrease in red blood cell production or anemia in female patients. This indicates that high levels of inflammatory factors in women with long COVID negatively affect their blood production, according to Ilahi.
In addition, the researchers discovered sex hormone imbalances in patients with long COVID, finding decreased testosterone levels in affected women, and decreased estrogen in male patients, as well as decreased cortisol levels in both.
The researchers reported that women with low testosterone levels had higher levels of inflammation in their blood. The researchers hypothesize that testosterone usually helps control inflammation, so lower levels may make women more susceptible to persistent inflammatory responses. Lower testosterone levels were also associated with symptoms such as brain fog, depression, pain, and fatigue.
The results suggest that hormonal imbalance may play an important role in the development of long COVID, especially with regard to its effect on women, according to Ilahi.
These findings are similar, though not identical, to what has been found in chronic fatigue syndrome (of unknown cause), also known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which also disproportionately affects women. For example, anemia is not associated with chronic fatigue, but chronic inflammation is a hallmark of it.
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