Read Part three of the series.
The recently published Household Pulse Survey performed by the American Centers for Disease Control and Prevention (CDC) showed that more transgender individuals (26.3 %) have suffered from Long COVID than cisgender men (13.5 %) and cisgender women (21.8 %).
A transgender person is someone whose gender identity differs from their biological sex at birth. Someone whose gender identity matches their birth-sex is called cisgender.
A transgender person’s internal sense of their own gender does not align with the sex they were assigned at birth. If a person was assigned female at birth but identifies as male, they would be considered transgender or in this case a trans man. If this person identifies as female, the term cisgender or cis woman is used.
Transgender individuals may undergo a process of transitioning, which can include social, medical, or legal steps to align their gender presentation with their gender identity. Not all transgender individuals undergo the same steps, and the experience is highly individual. Transgender individuals who did not undergo hormone therapy retain the biological make up of their biological sex at birth and thus a similar immune system.
Research strongly suggests that sex-based differences in the immune system are related to sex chromosome linked genes and immune modulation by sex hormones. While the genetic makeup of a transgender individual will not be changed, gender affirming hormone therapy can change sex hormone levels and could thus impact the immune system.
In previous parts of this series, we have explained the role of estrogen as an immune stimulating hormone. This observation plays a role in understanding Long COVID in transgender individuals.
Higher estrogen levels correlate with less severe acute infections but higher incidences of autoimmunity and thus a higher amount of Long COVID cases.
What do we know about Long COVID in trans women?
Estrogen is the hormone many trans women use to transition to a female gender. In line with estrogen having immune stimulating properties, a few case studies have described the onset of autoimmune disorders in adult trans females after estrogen use. A feminized immune system could lead to trans women having similar incidences of Long COVID as cis women. However, long-term research focusing on the immunological aspects of trans people in general and Long COVID in particular is still minimal.
Trans women who did not undergo hormone therapy retain their male biological makeup and will likely experience similar health outcomes after COVID-19 as we have described for cis men in this blogpost.
Trans women are born without ovaries and with a male immune system. Hormone therapy can lead to changes in the immunological makeup.
What do we know about Long COVID in trans men?
Trans men who undergo masculinizing hormone therapy usually receive testosterone. Studies have shown that estrogen does not seem to rise to “make up” for the higher testosterone levels. On the contrary, the levels of estradiol (a type of estrogen hormones) significantly decrease after hormone therapy.
One study researching the effect of testosterone treatment in trans men reported higher inflammatory activity and lower antiviral immunity after masculinizing hormone therapy. This would suggest a male-like immune response as described here but a lot more research is needed to prove this assumption.
Trans men who did not undergo gender-affirming hormone therapy may experience the same COVID-19 and Long COVID incidence as cis women.
Trans men who do not receive hormone therapy will likely experience Long COVID similar to cis women. Hormone therapy with testosterone might lead to a male-like immune response.
Why was the reported incidence of Long COVID higher in trans individuals than cis females?
The impact of gender-affirming estrogen and testosterone therapy on immune system function is not fully understood. Despite increasing social awareness for trans individuals, they remain significantly underrepresented in scientific literature.
We have to point out, that the Household Pulse Survey is based on self-reporting. We can thus not determine whether Long COVID incidences are higher in the trans community or just perceived higher. This would not mean that trans individuals are misreporting their condition, but they might be identifying their symptoms more often as Long COVID than the cisgender population. However, this is one possible explanation out of many.
Most countries (including Switzerland) report COVID-19 incidences by biological sex and not by gender. The incidence for transgender individuals in these countries is therefore simply not known. Moreover, we did not find data displaying how many trans individuals participating in the American survey were of female biological sex and how many had undergone hormone therapy.
It has been shown that transgender individuals often avoid medical care out of fear of discrimination or mistreatment, which could correlate with the reported higher incidence of Long COVID cases in this population. However, this correlation has not been scientifically explored.
In summary, research on immune-mediated diseases including Long COVID is only just scraping the surface for transgender individuals on hormones. Neither infection susceptibility, autoimmunity nor vaccine responses are fully understood. While Altea cannot give satisfying answers to questions about Long COVID in transgender individuals, we hope this blogpost raises awareness to this under researched population.
Overview of disease incidence differences between cisgender males and females, versus transgender individuals. (Source: White et al.)
This was part four of the series. Read part one and two about the impact of Long COVID and associated diseases on female reproductive health and part three about reproductive health impacts in male individuals. The last part of this series will show preliminary data about how testosterone levels could play a role in all genders.
