Graphical abstract Highlights • Effect of sex hormones on COVID-19 outcome bias in males and females. • Effect of immunological factors on COVID-19 outcome bias in males and females. • Angiotensin-converting enzyme-2 (ACE2) system and COVID-19 outcome in males and females. • Correlation between smoking and COVID-19 incidence in males and females. • Possible therapeutic options for COVID-19. The severe form of COVID-19 has significant sex disparities, with high fatalities commonly reported among males than females. The incidence of COVID-19 has also been higher in males compared with their female counterparts. This trend could be attributed to a better responsive and robust immune system in females. Cytokine storm is one of the pathophysiological features of severe COVID-19, and it occurs as a result of over-activation of immune cells leading to severe inflammation and tissue damage. Nevertheless, it is well modulated in females compared to their male counterparts. Severe inflammation in males is reported to facilitate progression of mild to severe COVID-19. The sex hormones, estrogens and androgens which exist in varying functional levels respectively in females and males are cited as the underlying cause for the differential immune response to COVID-19. Evidence abounds that estrogen modulate the immune system to protect females from severe inflammation and for that matter severe COVID-19. On the contrary, androgen has been implicated in over-activation of immune cells, cytokine storm and the attendant severe inflammation, which perhaps predispose males to severe COVID-19. In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, Cytokine storm, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, Estrogen, ACE2, angiotensin-converting enzyme 2, SARS-CoV, severe acute respiratory syndrome coronavirus, androgen, WHO, World Health Organization, ICU, Intensive care unit, RNA, Ribonucleic acid, RAS, Renin-angiotensin system, ROS, reactive oxygen species, Angiotensin-converting enzyme-2 (ACE2), ACE, angiotensin-converting enzyme, HCoV-NL63, human coronavirus NL63, mRNA, messenger RNA, IFN-γ, Interferon-gamma, IL-6, interleukin 6, TMPRSS2, transmembrane protein serine 2, ADCC, antibody-dependent cellular cytotoxicity, TLR7, Toll-like receptor 7, ADT, Androgen deprivation therapy, JSTOR, Journal storage, E1, Estron, E2, Estradiol, E3, Estriol, ERs, Estrogen receptors, ERα, Estrogen receptor-alpha, ERβ, Estrogen receptor-beta, NKCs, Natural killer cells, CXCL8, C-X-C motif chemokine ligand 8, NF-kB, Nuclear factor kappa B, CCL2, C-C motif ligand 2, CXCL-1, C-X-C motif ligand 1, TLR8, Toll-like receptor 8, CD40L, CXCR3, C-X-C motif receptor 3, FcγRIIIA, Low affinity immunoglobulin gamma Fc region receptor III-A, H3N2, Influenza A virus subtype H3N2, H1N1, Influenza A virus subtype H1N1, Xp22, Chromosome X band p22, ADAM10, Metalloproteinase domain-containing protein 10, ADAM17, Metalloproteinase domain-containing protein 17, PDI, Protein disulfide isomerase, ePDI, Extra-endoplasmic reticulum PDI,