Males are at a Greater Risk for Developing Severe COVID-19 illness

Souradip Mallick, National Institute of Technology, Rourkela

In the last two decades, corona-viral diseases became a major public health issue, starting with the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2002 through 2003, then the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in 2012, and currently, the COVID-19 pandemic. It has been observed that male Covid-19 positive patients are likely to develop serious issues and get hospitalized, as compared to females. This sexual dimorphism has led some to the assumption that the male sex hormone, testosterone, may be a risk factor associated with the severity of COVID-19, while the female hormone estrogen may be protective.

The following study was carried out by a group of researchers at Barnes Jewish Hospital in St. Louis, Missouri, with around 143 patients who tested positive for COVID-19.

After the age of 30 years, the testosterone concentrations in men decline continuously by 1% to 2% each year. With lower serum testosterone concentrations many diseases appear like obesity, metabolic syndrome, and other chronic illnesses, such as type II diabetes, renal insufficiency, and chronic lung disease.  The severity of COVID-19 illness seems to coincide with the nadir of lifetime testosterone, and the co-morbidities present in the particular individuals also enhanced the COVID-19 severity. Studies among COVID-19 patients in the hospital have found that testosterone concentrations are lower in men requiring intensive care unit (ICU) admission or use of ventilators than in those with milder illness. Men with testosterone concentrations less than the reference range have chronically increased concentrations of inflammatory mediators. It has also been observed that the pattern of inflammation in individuals having COVID-19 differs from the individuals with influenza. Patients with COVID-19 have higher concentrations of a few cytokines like interleukin 6 [IL-6] and interleukin 1 receptor antagonist [IL-1ra], lower concentrations of most cytokines, and profound type I and type II interferon immune suppression. Hence a detailed investigation was carried out to understand the association of testosterone with disease severity and inflammation in patients with COVID-19. Testosterone concentrations among men with milder disease symptoms were still lower than the reference range. Approximately 89% of men who were admitted to the hospital had lesser testosterone concentrations as compared to the reference range. 

Thus it can be concluded that lower testosterone concentrations and increased estradiol to testosterone ratio during hospitalization were associated with disease severity, inflammation, and mortality in men with COVID-19. The study proposes that there can be approaches made that antagonize testosterone signaling or supplement estrogen level to cure men having severe COVID-19 infection. However, the experimental group of this study was not large enough to draw any strong inference on this.  Further studies and investigations need to be made to put such a theory into practice.

Also read: TERATOMA: A RARE TYPE OF TUMOUR

Reference:

1.  Dhindsa, S., Zhang, N., McPhaul, M. J., Wu, Z., Ghoshal, A. K., Erlich, E. C., Mani, K., Randolph, G. J., Edwards, J. R., Mudd, P. A., & Diwan, A. (2021). Association of Circulating Sex Hormones with Inflammation and Disease Severity in Patients With COVID-19. JAMA network open, 4(5), e2111398. https://doi.org/10.1001/jamanetworkopen.2021.11398

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