A new study from the Vall d'Hebron Research Institute (VHIR) links severe cases of COVID-19 in men to decreased testosterone levels. Until now, previous studies had determined that this hormone was related to the course of the disease, but this new research finds that knowing the variation of its concentration in blood can contribute to the decrease in mortality. The work, published in BMC Medicine and led by Dr. Rosanna Paciucci, principal investigator of the Clinical Biochemistry group at VHIR, advances the knowledge regarding the role that this marker can have to be used in the prediction of severe disease and mortality in male patients. The research has been carried out with the participation of Dr. Mónica Martínez Gallo from the Translational Immunology group at VHIR and Dr. Timothy Thomson, from the Institute of Molecular Biology of Barcelona (IBMB-CSIC). Researchers from other groups at VHIR and Universitat Autònoma de Barcelona (UAB) have also participated.

A precise understanding of the molecular and biological mechanisms that may explain the association of severe COVID-19 with male sex is still lacking. The study has found significant quantitative differences in biomarkers predictive of severity in male patients compared to female patients. The researchers were able to determine that changes in the blood concentration of testosterone in men with COVID-19 during the course of the disease is the strongest predictor of survival of all the biological and biochemical measures studied, including the single measure at patient admission. The study suggests that failure to restore testosterone levels is not only due to dysfunction in the central hormonal axis, but that the peripheral axis at the gonadal level is also affected.

In lethal cases, failure to restore physiological testosterone values is significantly associated with impaired differentiation and polarization of T helper lymphocytes and increased proinflammatory circulating classical monocytes.

This study demonstrates that androgens play a relevant role in disease severity in men and specifically testosterone is shown to have a significant role in regulating the immune system to cope with SARS-CoV-2. "Additionally, we have observed that patients who died, who have not been able to restore normal testosterone levels, present accumulation of androstenedione (testosterone source hormone), which could suggest peripheral damage at the gonadal level and not only at the level of the central hormonal axis," explains Emily Toscano, predoctoral researcher in the Clinical Biochemistry group at VHIR.

Although men and women present a similar risk of contracting the disease, men more frequently develop severe disease. Previous studies had already shown the association between male sex and the severity of infection by other coronaviruses (SARS-CoV and MERS-CoV). "Our observations find that serum testosterone concentration is the strongest predictor of survival and/or mortality in men with COVID-19 and could be key in predicting the evolution of patients," comments Dr. Paciucci. Thus, they suggest an important role of the hormone in the immune response to COVID-19.

"These results justify future experimental explorations to identify the relationship between testosterone and the severity of SARS-CoV-2 infection that may open the door to implement treatments to prevent severe cases and deaths," concludes Dr. Paciucci.