With more than 425 million infections and 5.8 million deaths to date, the coronavirus disease 2019 (COVID-19) pandemic brought on by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placed an unparalleled load on the world’s healthcare system (March 2022). There is a gender variation in disease severity across the globe, with women experiencing more mild infections than men.
The COVID-19 pandemic: what is it?
The first indication of a COVID-19 epidemic was found in the Chinese city of Wuhan in December 2019. SARS-CoV-2, an enveloped, positive-sense, single-stranded RNA virus from the human beta-coronavirus family, is the culprit responsible for COVID-19.
Despite the fact that over 80% of COVID-19 patients only experience minor symptoms, elderly individuals, patients with co-existing conditions, and patients with impaired immune systems are far more likely to experience serious infection.
A growing body of research indicates that having a significant COVID-19 is also an increased risk for men. The risk of dying from COVID-19 is thought to be 20% higher in males than in women. Men are also more likely than women to experience major complications that necessitate admission to an intensive care unit (ICU) and mechanical ventilation.
Why are males more likely than women to have severe COVID-19?
Numerous genetic, immunological, lifestyle, and behavioral factors may make males more susceptible to developing severe diseases.
genetic predisposition
The viral spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor on respiratory epithelial cells, which starts the SARS-CoV-2 infection process. The joining of the viral envelope with the host cell membrane and the passage of the viral RNA into the host cell comes next.
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According to the available data, the level of ACE2 expression in human lungs directly correlates with the severity of SARS-CoV-2 infection. Therefore, it is hypothesized that any living thing with increased ACE2 expression in alveolar epithelial cells may hasten viral entrance into the respiratory system.
Asian men express ACE2 in the lungs much more than Asian women do, according to single-cell RNA-sequencing analyses conducted in this regard. Men are therefore more vulnerable to SARS-CoV-2 infection than women due to the genetic expression and cellular distribution pattern of ACE2.
biological vulnerability
In comparison to men, women often show a stronger immunological response to viral or bacterial illness. This may be the result of women having two X chromosomes as opposed to the one found in men.
It is well known that the X chromosome increases the expression of critical immunological elements that support the induction of strong immune responses that control infections. Moreover, female sex hormones including progesterone and estrogen are essential for promoting immunological signaling and minimizing inflammation, respectively.
Evidence suggests that women respond to influenza vaccination by producing more antibodies than men. This demonstrates their ability to stimulate powerful immune responses against invasive infections. However, this unique aptitude can also render women more prone to autoimmune illnesses, in which the body’s immune system begins mistakenly attacking its own cells and tissues.
The human body’s innate immune system serves as the initial line of defense against any encroaching infections. Controlled interferon signaling activation causes the generation of pro-inflammatory cytokines and chemokines at the infection site as a part of the early innate immune response. For pathogens to be eliminated at the first stages of infection, a controlled inflammatory response is essential.
Hyperinflammation is regarded as the primary indicator of disease severity in COVID-19 patients. Uncontrolled type 1 interferon response activation has been reported to result in excessive cytokine production (cytokine storm) in severe COVID-19 patients, which causes severe lung injury and multiorgan failure.
Male individuals with moderate COVID-19 have higher plasma levels of pro-inflammatory cytokines and chemokines, as well as more non-classical monocyte activation, than female patients, according to a recent study on male and female patients with the condition. The same study also showed that female patients’ T cell responses are considerably more activated than male patients’ T cell responses.
A worse illness prognosis is linked to males’ inferior T-cell responses. However, there is no correlation between male patients’ stronger innate immune responses and worse disease outcomes. In contrast, these reactions increase the risk of severe COVID-19 in female patients.
According to the study’s findings, the researchers hypothesize that therapeutic approaches intended to stimulate T cell response in male patients and reduce an innate immune response in female patients may be beneficial.
lifestyle elements
Worldwide, men have been shown to consume alcohol and tobacco at comparatively higher rates. The differences in these lifestyle choices between men and women may contribute to gender differences in COVID-19 susceptibility. Additionally, men are more likely than women to engage in high-risk behaviors, which raises their risk of contracting COVID-19.
According to several research, women are more likely to comply with COVID-19-related control measures, such as social withdrawal, face mask use, hand washing, and movement restrictions. These COVID-19 suitable activities aid in preventing COVID-19 infection.
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Men may also be more susceptible to COVID-19 because of certain occupational risk factors in addition to lifestyle and behavioral variables. Male workers outnumber female workers by a wide margin in low-skilled industries like transportation, food processing, delivery, construction, and manufacturing. According to studies, people in these professions are more likely to die from severe COVID-19 and other illnesses.
