Research suggests that males and females experience long COVID symptoms differently, with studies showing that women are more likely to experience severe hormonal changes from the virus. Now, researchers are investigating whether hormonal replacement therapy could treat women with long COVID.

Silva J, Takahashi T, Wood J, et al. Sex differences in symptomatology and immune profiles of long COVID. Published online March 2, 2024.

 

 

Studying sex-based differences in long COVID

 

In a preprint article released on March 2, researchers note “strong sex differences in the frequencies and manifestations of long COVID (LC)” in both the symptom manifestation and organ activity.

Silva J, Takahashi T, Wood J, et al. Sex differences in symptomatology and immune profiles of long COVID. Published online March 2, 2024.

 

The researchers note that “[t]estosterone levels were significantly associated with lower symptom burden in LC participants over sex designation.” Additionally, females were more likely to develop LC after an acute COVID-19 infection and to experience more intense symptoms.

Silva J, Takahashi T, Wood J, et al. Sex differences in symptomatology and immune profiles of long COVID. Published online March 2, 2024.

 

“These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex,” the researchers write.

Silva J, Takahashi T, Wood J, et al. Sex differences in symptomatology and immune profiles of long COVID. Published online March 2, 2024.

 

Regarding organ activity, the researchers state that males with LC experienced:

• Decreased frequencies of monocyte and DC populations

• Elevated NK cells

• Plasma cytokines including IL-8 and TGF-β-family members

Females with LC experienced:

• Increased frequencies of exhausted T cells

• Cytokine-secreting T cells

• Higher antibody reactivity to latent herpes viruses, including EBV, HSV-2, and CMV

• Lower testosterone levels (compared to females without LC)

 

Sex-based differences in acute and long COVID-19

 

Researchers have noted sex-based differences in both the long and acute phases of COVID-19. In contrast to findings that females with LC experience more severe symptoms, males are reportedly more vulnerable to the effects of acute COVID-19. For both forms of the disease, researchers say they are still questioning why these differences exist—and that there may be more than one answer.

“Sex-specific risk and ultimately outcomes are multifactorial - a function of the complex interplay between biology, behaviour, and the wider determinants of health,” researchers state in a 2021 article published in The Lancet.

Stewart S, Newson L, Briggs TA, Grammatopoulos D, Young L, Gill P. Long covid risk - a signal to address sex hormones and women’s health. The Lancet Regional Health - Europe. 2021;11:100242.

 

 

Is hormonal replacement therapy recommended for long COVID now?

 

Similarities between LC and menopause symptoms in women “could lead to women with symptoms of the perimenopause and menopause being misdiagnosed with Long COVID,” the article states.

The disproportionate impact of LC—combined with other research on sex-based experiences during long COVID—suggests that hormonal therapy could arise as a potential intervention for females experiencing long COVID.

For now, however, there is not enough research to confirm whether or not this sex-specific treatment will be effective.

According to the recent study, “whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown.”

Silva J, Takahashi T, Wood J, et al. Sex differences in symptomatology and immune profiles of long COVID. Published online March 2, 2024.