Exploration of sex-specific and age-dependent COVID-19 fatality rate in Bangladesh population

Abstract

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.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Gender; Sex hormones; TLR7; TMPRSS2.

Figure 1

Cumulative rate of infection per 100000 population. A: In different age groups under the Coronavirus Disease-2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) hospitalization data (by September 5, 2020; https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html); B: In gender-based fatality rate under the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) hospitalization data (by September 5, 2020; https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html).

Figure 2

Percentage of rate of death per total infected cases. A: In different age groups in Bangladesh; B: In gender-based disparity in Bangladesh.

Figure 3

Percentage of selected underlying medical conditions under the coronavirus disease-2019-associated hospitalization surveillance network hospitalization data (by September 5, 2020; https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html).

Figure 4

Cumulative rate of infection per 100000 population in baseline characteristics under the coronavirus disease-2019-associated hospitalization surveillance network hospitalization data (by September 5, 2020; https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html).

Figure 5

The role of sex hormones and hormone therapies in modulating severe acute respiratory syndrome coronavirus 2 entry in host cells and immune response. The replication cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) begins when the virion binds to the host cell receptor, angiotensin-converting enzyme 2 (ACE2) via its spike protein S1 subunit. After receptor binding, the virus gains access to the cytosol by acid-dependent proteolytic cleavage of the S protein into S1 and S2 subunits by a furin, cathepsin, transmembrane serine protease 2 (TMPRSS2), or another protease, followed by S2-assisted fusion of the viral and cellular membranes. In this proposed model, androgens can upregulate the activity of TMPRSS2 which is necessary for the SARS-CoV-2 spike protein priming. Female sex hormones, estrogens might downregulate the ACE2 expression, which is used by SARS-CoV-2 for host cell entry. Androgens suppress the inflammatory responses by decreasing the activity of the peripheral blood mononuclear cells, as well as the release of inflammatory factors and cytokines, such as IL-1β, IL-2, TNF-α. Female sex hormones, estrogens and progesterone exert a protective effect on females, through direct antiviral activity or immune-mediated mechanisms. Estrogen receptors (ERα and ERβ) are expressed in a diverse array of immune cells (T, B, natural killer cells, macrophages, DCs, neutrophils) and modulates immune responses. SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ACE2: Angiotensin-converting enzyme 2; TMPRSS2: Transmembrane serine protease 2; ERs: Estrogen receptors.