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Learn More. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID patients.

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On the other hand, other factors eg, hormonal levels and immune functions also need to be addressed due to the effects of sex differences on the outcomes of COVID patients. An insight into the underlying causes of sex differences in COVID patients may provide an opportunity for better care of the patients or prevention of the disease. It is explained how sex can affect angiotensin converting enzyme-2 ACE2that is a key component for the pathogenesis of COVID, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes.

Furthermore, the available data about the impact of sex hormones on the immune functions Free sex 2 COVID cases are looked into. Several studies have shown that there is an association between the sex of COVID patients and fatality rates, as well as critically-ill status. Studies in China, South Korea, United States, and Italy have reported a similar trend of sex bias in fatality rates of COVID patients, representing that case fatality rates are higher in male patients than in female patients.

The World Health Organization WHO; Geneva, Switzerland indicated that a lower percentage of women who are infected with the virus will die in comparison with men 1.

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Moreover, male patients with comorbidities had a higher risk of developing a critically-ill status compared with men without comorbidities; whereas, there was no such association in women. However, it is reported that there was no difference regarding disease duration between men and women.

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Besides the different effects of COVID on the physical status of men and women, studies have shown that the same goes for mental health of people. Studies of general population indicated that women present more mental disorders symptoms compared to men during the COVID pandemic, including s of depression, anxiety, post-traumatic stress symptoms, and decreased sleep quality. Additionally, attention should be paid to other factors which are or may be related to this sex bias in fatality rates of COVID patients, including hormonal levels, immune functions, comorbidities, and related conditions, as well as gender-related factors, including lifestyle and socioeconomic aspects.

Since X-chromosome encodes some genes related to immune responses, women have a lower level of viral load and less inflammation compared to men. Besides, after infection with viral agents, women produce lower levels of interleukin-6 IL-6 compared to men, which is associated with better longevity.

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Investigations have indicated that aging men have a reduced testosterone level, which is related to an elevated pro-inflammatory condition. Androgen receptor AR is involved in the regulation of both innate and adaptive immune responses, including the macrophage and neutrophil recruitment which is related to COVID While this observation applies to both sexes, estrogen therapy has resulted in the suppression of inflammatory processes and reduction of virus titers in animal models. However, the levels of TT and cFT were positively associated with the lymphocyte count.

However, its levels increase in boys with their growth and women have a lower level of sACE2 than men from the of Experimental animal studies have indicated that in kidney and adipose tissue, E2 enhances the activity and expression of ACE2. However, this study has some limitations.

First of all, not all published papers are in English, and Free sex 2 had to be excluded from this review. Besides, a ificant of studies concerning COVID have not reported the disaggregated data of men and women due to the urgent need for rapid publications of the research. Furthermore, findings in this area are limited and there are not many large-scale studies reporting the sex differences in COVID patients and the reason for this difference.

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Thus, further studies are required to draw a conclusion. Studies of COVID patients have shown that men have a higher risk of developing to the severe form of the disease compared to women. Moreover, case fatalities are higher in male patients than female patients.

An insight into the sex differences in covid patients: what are the possible causes?

Therefore, more attention should be paid to sex as an important variable. This study shows that different levels of ACE2 in men and women, the effects of testosterone on ACE2 levels, and the fact that the ACE2 gene is located on the X-chromosome should not be ignored. Furthermore, the effects of sex on immune responses and data available on the sex differences in COVID patients and immune system are summarized.

However, findings in this area are limited and further studies are required to draw a conclusion. PMD and ZA contributed in conception, de, and drafting of the manuscript.

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All authors approved the final version for submission. National Center for Biotechnology InformationU. Prehosp Disaster Med. Published online Jun Parisa Maleki Dana 1.

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Fatemeh Sadoughi 1. Jamal Hallajzadeh 2.

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Zatollah Asemi 1. Mohammad Ali Mansournia 3. Bahman Yousefi 4.

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Mansooreh Momen-Heravi 6. Author information Article notes Copyright and information Disclaimer.

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This article has been cited by other articles in PMC. Limitations However, this study has some limitations. Conclusions Studies of COVID patients have shown that men have a higher risk of developing to the severe form of the disease compared to women.

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Conflicts of interest The authors declare no conflict of interest. References 1.

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Clinical characteristics of deceased patients with coronavirus disease retrospective study. Clin Infect Dis. Epub ahead of print. Radiol Med. The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health. Int J Gen Med. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do?

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Am J Epidemiol. Int J Mol Sci. Front Public Health. Sex-specific clinical characteristics and prognosis of coronavirus disease infection in Wuhan, China: a retrospective study of severe patients. PLoS Pathog.

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Clinical and epidemiological characteristics of 1, European patients with mild-to-moderate coronavirus disease J Intern Med. Psychiatry Res. Immediate psychological responses and associated factors during the initial stage of the coronavirus disease COVID epidemic among the general population in China.

Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID pandemic: a systematic review and meta-analysis. Brain Behav Immun.

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Ann Intern Med. Conti P, Younes A. J Biol Regul Homeost Agents. Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab.

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The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest. The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male. Pozzilli P, Lenzi A. Androgen receptor influences on body defense system via modulation of innate and adaptive immune systems: lessons from conditional AR knockout mice. Am J Pathol.

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