• TMPRSS2 expression is several times higher in the prostate compared with any other tissue, as well as the upper digestive and respiratory tract.
• ESR2 is also found in the prostate, lungs, breast, and the cardiovascular system with implications in blood clotting. TMPRSS2 acts like the shape of the keyhole, while ACE2 is the actual lock. A higher expression of TMPRSS2 means a better keyhole fit for viruses
• In a study looking at the Italian population, expression levels of both ACE2 and TMPRSS2 were assessed. Researchers found no significant evidence that ACE2 is associated with COVID-19 severity or sex bias in the Italian population

However, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients. Genes related to higher levels of TMPRSS2 were more frequent in Italians vs. East Asian populations.

• Research has found that the expression of the fusion gene TMPRSS2:ERG, which is thought to be responsible for up to 80% of prostate cancers, is repressed by estrogen receptor beta (ESR2 gene) agonists. Phytoestrogens are agonists known to have up to 30-fold greater affinity for estrogen receptor beta.

DECREASING THE EXPRESSION OF TMPRSS2

• Phytoestrogens, curcumin, and lycopene (tomato sauce)
• Research has shown that curcumin binds to receptor-binding domain site of viral S protein and also to the viral attachment sites of ACE2 receptor and downregulates TMPRSS2, demonstrating that curcumin can act as potential inhibitory agent antagonizing the entry of SARS-CoV2 viral protein.

Variants in the ESR2 gene increase the need for phytoestrogens for prostate and breast health. Post-menopausal women will also benefit from increasing phytoestrogen intake.