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

• Published in: Frontiers in Endocrinology
• Main Authors: Flavia Tramontana, Sofia Battisti, Nicola Napoli, Rocky Strollo
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-12-01
• Subjects: COVID-19; sex hormones; immuno-endocrinology; immune response; estrogen
• Online Access: https://www.frontiersin.org/articles/10.3389/fendo.2021.726696/full

Epidemiological evidence shows clear gender disparities in the Coronavirus 2019 Disease (COVID-19) severity and fatality. This may reflect the contribution of gender-related factors, such as sex hormones, to COVID-19 pathogenesis. However, the mechanism linking gender disparities to COVID-19 severity is still poorly understood. In this review, we will pinpoint several elements involved in COVID-19 pathogenesis that are regulated by the two main sex hormones, estrogen and androgen. These include tissue specific gene regulation of SARS-CoV2 entry factors, innate and adaptive immune responses to infection, immunometabolism, and susceptibility to tissue injury by cytopathic effect or hyper-inflammatory response. We will discuss the mechanistic link between sex hormone regulation of COVID-19 pathogenetic factors and disease severity. Finally, we will summarize current evidence from clinical studies and trials targeting sex hormones and their signalling in COVID-19. A better understanding of the role of sex hormones in COVID-19 may identify targets for therapeutic intervention and allow optimization of treatment outcomes towards gender-based personalised medicine.