Androgen hormones may exacerbate sex differences in COVID-19 outcomes

A drug commonly prescribed for high blood pressure and other cardiovascular diseases, called spironolactone, reduced vascular inflammation and hormone-related vascular damage in a pre-clinical study of COVID-19.

The new publication, in the journal Viruses, helps researchers better understand why men have worse outcomes than women after contracting COVID-19, said first author Nitin Kumar, Ph.D., a postdoctoral researcher in internal medicine and human genetics at University of Michigan Health.

Kumar and colleagues, led by senior author Santhi Ganesh, M.D., an associate professor of internal medicine and human genetics at the U-M Health Frankel Cardiovascular Center, tested human endothelial cells that line arteries, and blood from participants who were hospitalized with COVID-19.

In the experiments, exposing the human endothelial cells to the androgen hormone DHT, typically found in larger amounts in men than in women, made the inflammation and vascular damage induced by the SARS-CoV-2 spike protein worse.

"We were able to block this effect with the drug spironolactone," Kumar said. "We are now working with other groups to facilitate the next steps of clinical trials and mechanistic research funding to follow up on our findings."

The Frankel CVC's M-BRISC program (Michigan Biological Research Initiative on Sex Differences in Cardiovascular Disease) funded this work.

Paper cited: "SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism," Viruses. DOI: 10.3390/v13112209