SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism

November 2021 in “ Viruses ”

Nitin Kumar, Yu Zuo, Srilakshmi Yalavarthi, Kristina L. Hunker, Jason S. Knight, Yogendra Kanthi, T. Andrea, Santhi K. Ganesh

dihydrotestosterone SARS-CoV-2 spike protein endothelial injury E-selectin VCAM-1 ICAM-1 TNF-α mineralocorticoid receptor antagonist spironolactone DHT COVID-19

TLDR Spironolactone may help reduce COVID-19 severity in men by blocking harmful effects of certain hormones.

The study examined the impact of the SARS-CoV-2 spike protein S1 on endothelial cells, revealing that dihydrotestosterone (DHT) worsened endothelial injury and inflammation, as indicated by increased markers like VCAM-1 and E-selectin. Spironolactone, a mineralocorticoid receptor antagonist, effectively reduced these effects, suggesting its potential as a treatment for COVID-19-related vascular damage. The research highlighted sex differences, with men showing higher levels of endothelial injury markers, possibly due to androgen signaling. The study involved 242 patients, providing a substantial sample size to support these findings and the potential therapeutic role of spironolactone in COVID-19.

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SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism

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