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Androgens May Explain Male Vulnerability to COVID-19

Among another 79,661 patients in the Veneto region with cancer other than prostate cancer, 312 developed COVID-19 and 57 died.

“This is the first paper to suggest a link between ADT and COVID-19,” commented lead author Andrea Alimonti, MD, PhD, Università della Svizzera Italiana in Lugano, Switzerland.

“Patients with prostate cancer receiving ADT had a significant fourfold reduced risk of COVID-19 infections compared to patients who did not receive ADT. An even greater difference (fivefold reduction in risk) was found when we compared prostate cancer patients receiving ADT to patients with any other type of cancer,” he said.

The finding raises “the hypothesis that androgen levels can facilitate coronavirus infections and increase the severity of symptoms, as has been seen in male patients,” he said.

“These data are very interesting and raise a fascinating hypothesis,” said Richard Martin, PhD, professor of clinical epidemiology at the University of Bristol, UK, commenting about the study. “But they do need independent validation in other large population-wide datasets…with appropriate statistical analysis including adjustment for important risk factors for SARS-CoV-2.”

He noted that the Italian study results were not adjusted for potential confounders, for example, age, body mass index, and cardiometabolic comorbidities, that are strong risk factors for SARS-CoV-2. In addition, men taking ADT may have been more likely to self-isolate and so be at reduced risk of getting the infection, he suggested.

How Do Androgens Interact With the Virus?

Alimonti and colleagues offer a mechanistic explanation of how androgens interact with the virus.  

Coronavirus gains entry into the human cell by binding its viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2. TMPRSS2 is a member of a family of proteins called type II transmembrane serine proteases, which are involved in a number of processes including cancer and viral infections, they explain.

“Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression,” they point out.

There is also evidence that the same androgen receptor regulates TMPRSS2 expression in nonprostatic tissues, including the lung.

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