Response to Letter Regarding Androgen Receptor PolyQ Alleles and COVID-19

The authors of the original publication respond to a letter to the editor by clarifying that 5α-reductase inhibitors (5αRi) like Dutasteride (Dut) do not deplete androgen levels, as Dut increases both tissue and serum testosterone (T), which maintains androgen receptor (AR) activation. They argue that the positive effects observed in the AndroCoV trial with Dut-treated individuals are not due to changes in T levels or activity. They also note that viral clearance is mostly complete within seven days of infection, suggesting that the time-to-remission outcomes measured after 7-10 days in the AndroCoV trial are more related to immune response and endothelial damage rather than viral presence. The authors reaffirm their hypothesis that shorter AR polyQ alleles are associated with less aggressive COVID-19 due to a beneficial immune-modulatory effect, contrasting with another study that suggests longer AR CAG repeats might be more active in the lungs due to local biological factors. They dispute this by pointing out that longer CAG repeats are associated with androgen insensitivity in all tissues, as seen in Kennedy's disease, and not increased transcriptional activity in specific environments like the lungs.