According to the World Health Organization, there have been over 760 million cases and 6.9 million deaths of Covid-19 globally since December 2019. Interestingly, men and women have been shown to react to Covid-19 infection differently, with men making up a higher share of hospital admissions, intensive care unit admissions, and deaths, despite similarities in case numbers, according to The Global Health 50/50 research initiative. Conversely, women have been shown to be at a higher risk of long Covid, whereby symptoms of Covid-19 last longer than 12 weeks. There have been multiple explanations put forward for this sex difference, one of which is that sex hormones alter the immune system. However, this has been difficult to assess as researchers might not know whether the sex hormones alter, or are altered by, the immune system. Despite this, in research published in September 2024 in Nature, Tadepally Lakshmikanth and colleagues were able to explore this association by focusing on people undergoing gender-affirming hormone therapy and found that testosterone plays a key role in regulating the immune response, which may explain sex differences for Covid-19.
To directly observe the influence testosterone had, this clinical study conducted longitudinal blood sampling of 23 trans men (people who identify as male but were assigned female at birth) aged 18–37 years undergoing gender-affirming hormone therapy with testosterone. Blood samples were taken when testosterone treatment began, then three and 12 months after. By analysing proteins involved with the immune response and immune cells within the blood samples, the researchers were able to notice how they changed in response to testosterone treatment. It was found that testosterone is responsible for regulating the balance of two immune signalling systems, type-1 interferon and tumour necrosis factor, which in turn alters the immune response. As testosterone was found to cause an upregulation of certain immune response signals, researchers theorised that this could result in an extreme inflammatory response called a cytokine storm, which can cause mortality in Covid-19. Therefore, this may explain why men and women react differently to Covid-19 infection, and the increased mortality for men.
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This study not only helps researchers understand the difference in immune responses between the sexes but is also something crucial to consider for people receiving hormone therapy, as they may be more vulnerable to severe Covid-19 infection, thus could possibly even be a potential target population for vaccines. However, the sample size of this study was very small, therefore larger-scale studies are needed to validate these findings. Vaccination coverage for the primary vaccination course of Covid-19 in the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan) is expected to increase slightly, with GlobalData epidemiologists predicting coverage for men and women of all ages will increase from 73.5% in 2024 to 74.10% in 2026. The same trend is expected for those who have received the first booster dose and the second booster dose, whereby coverage is expected to increase from 51.1% (2024) to 51.6% (2026), and 43.5% (2023) to 44.9% (2026), respectively.
