Throughout history, pandemics have been a scourge for humanity. The COVID-19 pandemic, which started in late 2019, has claimed more than 5 million lives as of November 2021, and infected around 250 million people worldwide.

However, gender disparities in viral immunity and susceptibility have emerged; men are more susceptible to viral infections, and suffer more severe symptoms than women. But why is this? This article dives into the gender gap in viral immunity, exploring why men are more vulnerable to viral sickness than women.

The Biology of Viral Infections

Viral infections occur when an external microorganism enters the host body (the person afflicted with the virus). A virus has two primary components: genetic material, the DNA or RNA; and a protein coat that encases the genetic material.

Viruses depend on host cells to replicate and grow; they invade host cells, use the host cells’ machinery to copy themselves, and then release new virions, or immature viruses, to infect healthy cells and continue the cycle of infection.

The immune system recognizes the invading virus and mounts a counter-response to eradicate it. However, virus-host interactions can lead to varying effects on host cells.

Some viruses remain latent, hidden from the immune system in cells, and do not elicit the immune response. Others, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spike proteins bind to angiotensin-converting enzyme 2 (ACE2) receptors in the respiratory tract and replicate in the lungs, triggering an immune response in the lungs.

Immunology and Viral Infections

Your immune system has two primary lines of defense against a viral infection: the innate immune system and the adaptive immune system.

The innate immune system, the first defense line, represents nonspecific immune mechanisms such as natural barriers (skin, mucous membranes), interferons, and natural killer cells. The adaptive immune system is the second line of defense and represents our body’s memory of past infections.

When the immune system encounters a pathogen, it produces antibodies that recognize the pathogen and activate the immune system to respond. When the immune system encounters the same pathogen at a future date, the immune response is stronger and faster because of this previous exposure.

Researchers have found that men tend to have a weaker innate immune system response than women, whereas women tend to have a stronger adaptive immune response.

In other words, women’s immune systems are more likely to recognize and respond to a virus’s presence than men’s immune systems. One study found that a primary factor in this difference is sex hormones, with estrogen enhancing the immune response, while testosterone suppresses it.

Testosterone and Immune Responses

Testosterone, a sex hormone predominant in men, has been found to suppress immune responses. At clinical levels, testosterone treatment is known to reduce the inflammatory response as seen in autoimmune diseases such as arthritis or multiple sclerosis.

However, lower levels of testosterone can lead to lower immune system function and vulnerability to viral sicknesses. A study conducted in 2017 showed that the severity of influenza was higher in men when compared to women.

Another study conducted in 2014 revealed that testosterone performed a role in suppressing immune reactions, raising the vulnerability of men to various kinds of infectious diseases.

Estrogen and the Immune Response

Estrogen is one of the primary sex hormones present in women, helps to regulate the menstrual cycle, and encourages female physical characteristics.

Research in the past has inferred that estrogen might have some immunological properties and could serve to fortify the immune system.

Estrogen can bind to estrogen receptors pre-present in immune cells, encouraging the production of B cells, which help produce antibodies and protect against germs; and T cells, which combat infection and remove the potentially dangerous microbes that cause them.

Why Women Develop Autoimmune Diseases More Frequently?

Autoimmune illnesses are diseases in which your immune system mistakes healthy cells for foreign invaders and attacks them. Research shows that women are significantly more susceptible to chronic autoimmune diseases than men.

However, why this happens is still not fully understood. According to a study published in the journal of Nature Communications in 2020, testosterone-estrogen balance in men and women contributes to the gender gap in autoimmune diseases.

The hormone testosterone has immunosuppressive effects, so it serves as a defense mechanism against autoimmune diseases in men. However, women have higher estrogen levels, which can enhance immune reactivity and contribute to autoimmune disease susceptibility.

Age and Viral Infections

Age can also play a significant role in immunity. As we age, our immune system’s ability to recognize and fight pathogens declines. Older adults, especially those aged 85 years and above, tend to have weaker immune responses.

As a result, they are more susceptible to viral diseases like COVID-19 and influenza. This difference between the sexes increases with age, with women developing fewer severe respiratory infections compared to elderly men, where the mortality rate is higher.

Nature and Nurture

The different abilities to fight viral infections between the sexes are not entirely genetically determined. Research has shown that environmental and behavioral factors also play a role.

Men are more likely to smoke, drink alcohol, have sedentary lifestyles, and engage in occupation and activities that end in exposure to other infectious agents. Additionally, women, particularly caregivers, have more social contacts and a higher likelihood of being exposed to infectious agents. These factors influence the occurrence of viral infections in men and women.

Conclusion

The gender gap in viral immunity is a complex issue that is influenced by various biological, social, and environmental factors.

The difference in the response of the innate and adaptive immune systems, the impact of hormones, age, and lifestyle factors contribute significantly to the gender gap in viral immunity. It is essential to acknowledge these differences and tailor preventative and therapeutic interventions to be gender-specific. This measure can help reduce susceptibility and boost immune responses in men and women.