Peer-review started: October 26, 2020
First decision: November 16, 2020
Revised: November 20, 2020
Accepted: December 16, 2020
Article in press: December 16, 2020
Published online: January 28, 2021
Processing time: 93 Days and 3 Hours
Coronavirus disease-2019 (COVID-19), a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health emergency and a threat the entire world. The COVID-19 shows a wide spectrum of clinical presentations, severity, and fatality rates. Although the fatal outcomes of the COVID-19 pandemic are evident in all age groups, the most devastating impact on the health consequences and death from COVID-19 are associated with older adults, especially older men. COVID-19 pandemic is affecting different countries in the world especially in the 65+ years age male group. In fact, several genes involved into the regulation of the immune system are strategically placed on the X-chromosome and trigger a gendered mediated antiviral fight. The aim of this study is to explore and exploit whether a relationship exists between male sex and COVID-19 mortality and the relationship is age dependent. Herein we discuss the possible role of physiological and immunological sex differences into the higher morbidity and mortality of SARS-CoV-2 between females and males. Deciphering gender differences in COVID-19 offers a window into the principles of immunity against SARS-CoV-2 infection and this information on ageing dependent gender disparity might contribute to our current understanding of COVID-19 infection and disease treatment.
Core Tip: (1) Older age, male sex and acute illness severity are associated with increased mortality risk; (2) Older age, underlying co-morbidities, social deprivation and ethnicity have been associated with worse outcomes from coronavirus disease-2019 (COVID-19); (3) Sex hormones might be implicated in the age-dependent and sex-specific severity of COVID-19; (4) Male sex hormones usually appear as immunosuppressants, whereas female sex hormones enhances the actions of humoral immunity; and (5) Female sex hormones exert a protective effect of COVID-19 severity on females through direct antiviral activity or immune-mediated mechanisms.