Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease‐19 (COVID‐19): A scoping review

Abstract

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS‐CoV‐2 infection. From the experiences of Novel Coronavirus Disease‐19 to date, male patients are likely to suffer from high‐intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS‐CoV‐2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus‐derived T lymphocytes) and humoral immunity (antibodies).

Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy

“…Importantly, as mentioned above, no significant difference was reported to date between youngest male and female patients [ 5 ]. This could reinforce the hypothesis that sex hormones and their immunomodulating activity could play a role in adult Long COVID patients [ 18 , 19 ].…”

The Suppressor of Cytokine Signalling family of proteins and their potential impact on COVID‐19 disease progression

“… 59 This is shown in a study where it has suggested that the oestrogen receptor subtype, ER‐α that present only in female mice enhances TLRs and NK cells response, producing a much more robust cytokine response (TNF‐α, IL‐1 and IL‐6) compared to the male mice, causes the death of infected cells, thus, clearing the pathogen more efficiently. 60 Moreover, the predominant gender‐bias occurrence of transmembrane protease serine 2 (TMPRSS2) and ACE2 receptors in males may contribute to the high SARS‐CoV‐2 entry and replication. 60 Interestingly, the androgen receptors present only in males, are the promoters for TMPRSS2.…”

“… 60 Moreover, the predominant gender‐bias occurrence of transmembrane protease serine 2 (TMPRSS2) and ACE2 receptors in males may contribute to the high SARS‐CoV‐2 entry and replication. 60 Interestingly, the androgen receptors present only in males, are the promoters for TMPRSS2. In contrast, females can regulate the expression of ACE2 via oestrogen activities.…”

“…In contrast, females can regulate the expression of ACE2 via oestrogen activities. 60 Hence, these conferred some immunoprotective measures to females compared to males.…”

Microbes, Clinical trials, Drug Discovery, and Vaccine Development: The Current Perspectives

“…This has recently been proven once again with the evolution and spread of hitherto a novel Coronavirus (CoV), which was believed to have emerged and spilled from the bats and pangolins to humans The cause for concern with these microbial emergences is the lack of preparedness among the people, no knowledge of the microbe's pathobiology, and other characteristic features that include the modes of transmission, the severity of infection, and the absence of specific antimicrobial agents or vaccines 13 . Also, it is crucial to understand that humans may not be sufficiently prepared to counter the effects of microbes when encountering novel microbes for the first time 14 . This has been proven from the experiences of the current SARS-CoV-2 pandemic, wherein the initial mortality rates were significantly higher than in the later stages of the pandemic 15 .…”