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Novel therapeutic approach against severe COVID-19 in males

On August 11, 2023, an international research team led by virologist Professor Gülşah Gabriel from the Leibniz Institute of Virology (LIV) and the University of Veterinary Medicine Hannover (TiHo) published a pioneering interdisciplinary study. In close collaboration with the University of Siena and other national and international research institutes as well as hospitals, the enzyme aromatase (CYP19A1) was identified as an important factor for severe COVID-19 courses in male patients. The results of this study are now published in the renowned journal Cell Reports Medicine.

Retrospective analyses of epidemiologic data have repeatedly shown that COVID-19 mortality is higher in males as compared to females. However, the underlying factors mediating sex specific disease outcome were largely unknown.

In this study, the interdisciplinary research team analyzed genetic data obtained from 2,866 COVID-19 patients and identified a mutation in the CYP19A1 gene that is associated with an increased risk for hospitalization in male patients. CYP19A1 plays a key role in testosterone metabolism. Lung samples analyzed from deceased COVID-19 patients also showed increased expression of the CYP19A1 gene in male patients compared to female patients. These findings suggest that this gene is involved in sex-differences observed in COVID-19 outcome.

"This collaborative work stresses the importance of host genetics in understanding molecular mechanisms of severity and treatment of viral disorders", says Professor Alessandra Renieri of the University of Siena who provided the genetic data of the large COVID-19 cohort.

Preclinical studies in animals models confirmed these findings. Treatment of SARS-CoV-2-infected animals with the aromatase inhibitor letrozole improved long-term lung function and restored hormonal balance, particularly in male animals. This suggests that aromatase inhibitors may provide a promising therapeutic strategy for the treatment of male COVID-19 patients.

Professor Gülşah Gabriel confirms the importance of international and interdisciplinary collaboration and highlights, "Our collaborative findings may form a basis for individualized therapeutic strategies against COVID-19".

Scientific contact:

Prof. Gülşah Gabriel
guelsah.gabriel(at)leibniz-liv.de   
Leibniz Institute of Virology, Hamburg
University of Veterinary Medicine, Hannover