Immuno-Endocrinology of COVID-19: The Key Role of Sex Hormones

The document discusses the influence of sex hormones on the severity and progression of COVID-19. Males are twice as likely to develop severe or fatal disease compared to females, possibly due to the impact of sex hormones. Estrogen and androgen, the two main sex steroids, regulate several elements involved in COVID-19 pathogenesis, including immune responses and susceptibility to tissue injury. Estrogen tends to downregulate the SARS-CoV-2 main receptor, while testosterone may enhance its expression and promote viral replication. The response to COVID-19 vaccines may also vary by gender, with females often showing a more robust antibody response. However, a meta-analysis showed a 33% reduced risk of developing COVID-19 in males. The balance of androgen to estrogen may modulate the virus-host interaction and immune response, with estrogen enhancing anti-viral defenses and immune activity while androgen displays immunosuppressive action. More large-scale studies are needed to fully understand these effects.