While men & women have the same prevalence of COVID19, male patients have a higher mortality. COVID-19 case-fatality ratio is approximately 2.4 times higher among men than among women.
Men and women differ in both innate and adaptive immune responses, perhaps related in part to sex-specific inflammatory responses resulting from X-chromosomal inheritance. The X chromosome contains a high density of immune-related genes; therefore, women generally mount stronger innate and adaptive immune responses than men. Men have higher plasma ACE2 levels than women do, and a recent study of patients with heart failure showed that plasma ACE2 concentrations were higher than normal in men and higher in men than in women, possibly reflecting higher tissue expression of the ACE2 receptor for SARS‐CoV infections. This could explain why men might be more susceptible to infection with, or the consequences of, SARS-CoV-2.
Menassel Kawther added a reply on October 3, 2020, as follows:
"أعتقد أنه لا يمكن حسم المسألة حاليا سيكون الحكم سابق لأوانه "
Rough translation into English: " I think it can't be resolved right now. It's going to be premature [to answer this question] right now."
In my view, this reply prioritizes a scientific approach that is actuarial, that is, this answer favors a statistical analysis of a large amount of numerical data with wide parameters both in space and time, i.e., a generous sampling of abundant numbers of men and women who are located in various geographical locations and who are studied during a specified number of months or even years before any conclusions are drawn about whether the novel COVID-19 virus afflicts men (or women) with greater severity than the opposite sex.
Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In a review, researchers explored sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498997/
The high mortality of males due to COVID-19 raises the question whether males are more vulnerable than females. Males show higher mortality from diseases including heart disease, diabetes, liver disease, and cancer. Since these diseases are known to show sex-specific occurrence, they could be contributing factors for the sex-biased mortality from COVID-19. For instance, the male mortality in Italy was reported to be high compared to China and this is suggested to be due to a higher prevalence of cardiovascular diseases in Italian men. The differences between males and females are observed not only in disease susceptibility but also in early development during infancy, endurance towards stress conditions, and overall life expectancy. Sex differences are observed in life expectancy, with females outliving males by almost 7 years in some countries. This difference in life expectancy may be due to sex-related differences including hormonal milieu, genetics, and other physiological traits. Pieces of evidence indicate that females can outlive males even in harsh climate including famine. The 1772–1773 famine in Sweden dropped the life expectancy of males to 17.15 years while it was 18.79 years for females. The Irish famine (1845–1849) dropped life expectancy to 18.7 years for men and 22.4 years for women. The Ukrainian famine in 1993 dropped the life expectancy of males from 41.58 to 7.3 years and 45.93 to 10.9 for females. Other historical events also suggest that endurance levels to cope up with stressful conditions are low in males compared to females. The freed American slaves’ journey back to Africa in 1820–1843 resulted in high mortality with 43% death rate in the first year. The life expectancy at birth was 1.68 years for males and 2.23 years for females. The measles outbreak in Iceland (1845–1849) also showed sex-specific mortality. The average life expectancy dropped from 37.62 years to 16.76 for males and 43.99 years to 18.83 years for females. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498997/
Taken together, it can be suggested that males have lower endurance levels than females. The sex-related difference in the immune system, sex hormone milieu, and other unknown causes may be a contributing factor for the high mortality of males in stressful conditions including COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498997/
COVID-19 has shown a clear male-biased severity and mortality in different countries. The sex-biased pathogenesis is not understood properly, but it could be multifactorial. The difference in immune system function between males and females could be an important determinant. Females are known to show a robust immune response to pathogens which could help them to better regulate viral load and viral clearance compared with males. Since many immune genes are present on X chromosome, the XX and XY genetic constitutions could also contribute to COVID-19 severity. Other differences including steroid hormone milieu and sex organs could also play a crucial role in pathogenesis (Fig. (Fig.5).5). Estrogen in females can have immune-enhancing effects while testosterone secreted by the testis can have immune-suppressive effects. However, there is no sufficient clinical data to show that the SARS-CoV-2 can enter the testis and regulate COVID-19 severity and mortality in males. Hence, testis involvement should be further explored to understand male-biased mortality. The stress endurance level in males and females is also different with females showing higher endurance against different stress including food shortage and pathogens. This could also be a contributing factor in sex-biased pathogenesis from COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498997/
Dear Dr Amina Sultan . COVID-19 may be associated with worse outcomes in males than in females. However, until more detailed data are provided in further studies enabling adjusted analysis, this remains an unproven assumption. See the RG link: Article COVID-19 gender susceptibility and outcomes: A systematic review
Initially COVID-19 was more severe in men. However, more recently in Saudi Arabia the gender distribution has equalized. The reasons for this are unclear. However, there may be a difference in vaccine uptake between genders.
Men are more at risk for worse outcomes and death, independent of age, with COVID-19. While males and females have the same prevalence of COVID-19, male patients have a higher mortality.Apr 29, 2020
https://www.frontiersin.org › full
Gender Differences in Patients With COVID-19: Focus on Severity and ...
Since TLR7 gene is located on the X chromosome, mutations in TLR7 will affect males more than females, who bear two X chromosomes per cell. TLR7 deficiency has been reported as a genetic mediator for severe COVID-19 especially in males.
Article Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effe...
Several hypotheses have been postulated to explain the greater severity and the less favorable outcome of COVID-19 in men compared to women. Differences in cultural and social behaviors in men and women have been claimed, together with the presence of comorbidities, such as cardiovascular and respiratory diseases, as well as smoking habits and alcohol intake, which are generally more prevalent in men compared to women. Furthermore, the disparities between sexes has been also attributed to the evidence that men adhere to hygiene practices, including simple handwashing behavior, less rigorously and assiduously than women, with consequent easier infection and burden of the disease in men compared to women. Besides these considerations, an increasing body of evidence indicates that the sex-related difference in the severity and outcome in COVID-19 patients is mainly ascribable to mechanisms of virus infection, immune response to the virus, development of hyperinflammation and hypercoagulability, and/or systemic inflammation and thromboembolism.