CME INDIA FEATURE – Presented by Dr N.K. Singh – Admin, CME INDIA
Men vs Women death rate in COVID19
- The early reports of COVID-19 cases and deaths in India suggests that males are at a greater disadvantage than females with CFR of 3.3% and 2.9%, respectively
- Early evidence indicates that males have higher overall burden, but females have a higher relative-risk of COVID-19 mortality in India. Elderly males and females both display high mortality risk and require special care when infected [J Glob Health Sci. 2020 Jun;2(1): e17.Published online Jun 02, 2020. https://doi.org/10.35500/jghs.2020.2.e17]
- Available data suggest that While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age. A consistent pattern which has emerged of higher death rates among men compared to women infected with COVID-19 is palpable worldwide. Data shows that men are roughly twice as likely to die from a COVID-19-related illness than women are. (A recent study in Frontiers in Public Health concluded that men are at least twice as likely to die of COVID-19, regardless of age. Men were also less likely to survive critical cases of COVID-19)
- So the COVID-19 pandemic has raised many questions and science is still at loss to understand the mystery.
- Worth to note that India and many other countries do not report their COVID-19 cases and deaths separately for women and men. So it is difficult to do an independent analysis.
Solving the Mystery of Sex Discrimination:
- Hormonal: It has been speculated that effects of sex hormones testosterone, oestrogen or progesterone may be responsible. Study finds menstrual status, hormones may help explain sex bias in SARS-CoV-2 infection outcomes. Findings, published in Clinical Infectious Diseases, suggest that anti-Müllerian hormone (AMH) and estradiol (E2) were potential protective factors, negatively correlated with COVID-19 severity, with E2 possibly exerting its effect by regulating cytokines linked to immunity and inflammation. The study also found that menopause was an independent risk factor for female COVID-19 patients.
- Genetic: Scientists are working on genetic makeup and its association.
- Immune response: Whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. One recent article published online on 28th August in Nature journal has tried to demystify it.
A more vigorous immune response in women increases the capacity to fight off an infection, as well as the risk of autoimmune diseases. Early studies also report a higher number of antibodies of the sub-type IgG in women compared to men after a SARS-CoV2 infection sets in. There is also evidence that mast cells in women can initiate a more active immune response, which helps better fight infectious diseases.
Their results revealed key differences in immune responses during the disease course of SARS-CoV-2 infection in male and female patients.
It was found that the levels of several important proinflammatory innate immune chemokines and cytokines such as IL-8, IL-18 (at base-line), and CCL5 (longitudinal analysis) were higher in male patients, which correlated with higher non-classical monocytes (at baseline).
Researchers observed a more robust T cell response among female patients compared to male patients at baseline. In particular, activated CD8 T cells were significantly elevated only in female patients but not in male patients over healthy volunteers. Analysis of their clinical trajectory revealed that, while poor T cell responses were associated with future progression of disease in male patients, higher innate immune cytokine levels were associated with worsening of COVID-19 disease in female patients. Importantly, the T cell response was significantly and negatively correlated with patients’ age in male, but not female, patients. These data indicate key differences in the baseline immune capabilities in men and women during the early phase of SARS-COV-2 infection, and suggest a potential immunological underpinning of the distinct mechanisms of disease progression between sexes.
Collectively, their data suggest that vaccines and therapies to elevate T cell immune response to SARS-CoV-2 might be warranted for male patients, while female patients might benefit from therapies that dampen innate immune activation early during disease. Immune landscape in COVID-19 patients is considerably different between the sexes, and these differences may underlie heightened disease susceptibility in men.
[Published online 26 August 2020Takahashi, T. et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature https://doi.org/10.1038/s41586-020-2700-3 (2020).]
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