What Does Biological Sex Refer To?
Biological or assigned sex refers to the sex assigned to a person at birth or the type of reproductive cells or gametes they produce. The gametes produced by an individual may be male or female, or in some cases, both. It is often referred to as the condition of being male or female.
The determining factors for biological sex are:
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Sex Chromosomes- XX, XY.
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Reproductive Tissue- Ovaries, testes.
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Sex Hormones- Estrogen, progesterone, testosterone.
How Is Biological Sex Related to Diseases?
The life spans and illness patterns that affect males and females may vary. Biological sex is therefore considered an important distinction when it comes to understanding disease exposure, susceptibility, metabolic changes, and responses to diseases. Sex differences have been noted for both energy metabolism and therapeutic responses. That is why it is necessary to understand the differing susceptibilities of males and females to diseases and to drugs they are given for these diseases, since their responses may vary on the basis of metabolism. One of the typical epidemiological variables considered in any disease is biological sex-based predilection for the disease. Males of a certain age or of all age groups may be affected to a greater degree than their female counterparts by some diseases, while the opposite may hold true for others. In certain cases, there may be no discernible differences between male and female responses to diseases.
How Has Biological Sex Been Related to Epidemics in the Past?
Previous instances of epidemics such as SARS (severe acute respiratory syndrome) and MERS (Middle Eastern respiratory syndrome) have indicated male predominance. There has been a consistent tendency for males to be more severely affected than females.
When Is COVID-19 Considered Severe?
COVID-19 has been determined to be severe on the basis of the following factors:
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Hospitalization.
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Admission to intensive care units (ICUs).
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Fatality rates.
How Is Biological Sex Related to COVID-19?
The COVID-19 pandemic has caused infections and deaths in massive numbers. Current understanding of COVID-19 has covered everything from comorbid disorders (disorders that may already exist in a patient, which can increase their susceptibility to COVID) to other risk factors. Among the risk factors or predisposing factors is gender (or more specifically, biological sex).
How Has Biological Sex Impacted COVID-19 Severity?
Males appear to be most affected by COVID-19, as evidenced by various studies and reports that have found a particularly high risk of mortality among males affected with COVID-19. While females may be equally susceptible to developing COVID-19, its mortality rate is skewed in favor of the male ratio. The case fatality rates as reported by numerous studies that have taken place over the course of the pandemic have almost all displayed a gender-wise distinction. It appears that hospitalization, ICU admissions, and deaths related to COVID have been noted more commonly among men than women. While the elderly have had almost similarly increasing mortality rates, people over 30 have in general demonstrated a higher risk among males than females.
What Are the Possible Reasons for Biological Sex-Based Differences in Infection Manifestation?
The reasons for biological sex-based differences in infection severity may range from their personal habits and health behaviors to their biological differences on the basis of hormones and other factors.
They include:
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Habits - Greater substance abuse issues among men than women.
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Health Behaviors - Less tendency to seek out medical help for ailments among men.
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Age - Biological sex can cause changes in immunity, particularly in relation to the aging of the immune system due to sex steroid concentrations.
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Immune Response - Biological sex can affect immune responses, meaning that sex differences may exist in male and female reaction patterns to infections. The Y chromosome in males has immunoregulatory functions that can impact influenza virus infections. Sex steroids may also contribute in some manner. Immune cells in males may respond in a different manner than females when exposed to agents that stimulate immune responses.
What Are the Possible Reasons for Biological Sex-Based Differences in COVID-19 Manifestation?
When it comes to COVID-19, the biological differences that have an effect on disease severity are impacted by angiotensin-converting enzymes (ACE 2).
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ACE2 is the receptor used by SARS-CoV-2 (the COVID-causing virus) for entry into human cells. The ACE2 protein is commonly found in the heart, kidneys, testes, and lungs. In COVID-19, it is the lungs that are mainly affected. The S1 spike protein of the SARS-CoV-2 virus binds to the ACE2 receptor that is present in the lungs (specifically in the alveolar epithelial cells). In males, the expression of the ACE2 protein may be well over that of females, and this can cause differences in the outcomes of COVID-19 infection between sexes.
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Given the hormonal connection, there have been suggestions that estrogen acts as a protective factor in women affected by COVID-19. The mechanism by which it does this may be through reduction in the levels of the ACE2 receptor for SARS-CoV-2.
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The inflammatory, humoral immune and antiviral responses displayed by females are generally greater than males, meaning that their systems are cleared of the viruses (including COVID-19) sooner than males. This usually means better recovery among females. On the other hand, inflammatory immune responses among males in addition to cell counts in COVID-19 may also be greater in males, making them more susceptible to severe infections than females.
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Women apparently display better and earlier antibody responses than males. This means that antibodies (infection-fighting cells) are produced quite early during the infection, and progression of COVID-19 into a more severe form is less likely to happen.
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Comorbidities also have a bearing on gender-based expression of disease severity. The comorbid diseases that display the most susceptibility to COVID-19 include hypertension, diabetes, and obesity. While these comorbidities appear in almost similar numbers among both sexes, it is estimated that men are more likely to receive a diagnosis of hypertension or diabetes than women. These factors may also predispose to COVID-19 infection severity among men.
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In a revolutionary study that examined the sex differences mediated by immune responses to COVID-19, the sex biases observed were correlated to differences in immune responses. Higher levels of cytokines like IL-8 and IL-18 were noted in the plasma of male patients, while females showed robust activity of T cells. Poor T cell activity indicated worse outcomes for the disease in males but not in females. In contrast, poor activity of innate immune cytokines in females resulted in worse outcomes for them.
Conclusion:
The consensus from reports worldwide has been that men are more likely to be severely affected than women by COVID-19. While the mechanism by which male predilection occurs may not be fully understood, enough evidence does exist to be able to take an educated guess on the reasons. These factors that predispose to COVID-19 infection severity among men are good to know about because the knowledge allows for a modicum of control. It allows men to be able to identify the risk factors in their lives and control, treat, or eliminate these issues if possible. Thus, while there is a need for caution, there is also hope.
