COVID-19 Severity and Androgen Receptor Polymorphism

SIMPLE SUMMARY: Since the early stages of the COVID-19 pandemic, it was recognized that male patients risked a more severe form of the disease. This suggested that, among other factors, a genetic predisposition could justify this issue. Thus, we investigated the CAG repeat polymorphism of the Androgen Receptor gene in a group of 142 recovered patients. Reduced androgenic signaling predisposes men to a more severe form: low testosterone levels and reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19. ABSTRACT: During the COVID-19 pandemic, the most severe form of the disease was most often seen in male patients. The aim of this study was to identify any male predispositions that could be used to predict the outcome of the disease and enable early intervention. We investigated CAG polymorphism in the androgen receptor gene and serum levels of testosterone and LH, which were considered as probably responsible for this predisposition. The study involved 142 patients who had recovered from COVID-19 at least three months previously and were classified according to their disease severity using the World Health Organization (WHO) classification. We observed a significant increase in the number of CAG repeats with increasing disease severity: the percentage of patients with more than 23 repeats increased two-fold from Grade I to Grade IV. Furthermore, testosterone levels were significantly lower in patients with severe disease. Reduced androgenic signaling could predispose men to a more severe form: low testosterone levels and a reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19.