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Will Elevated Estrogens Level Reduce Fatality in COVID-19 Patients

30 April 2020   17:00 Diperbarui: 30 April 2020   17:01 227
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https://www.news-medical.net/health/Estradiol-and-Estrogen-Levels.aspx

The consequences of this excessive response are fatal and generally lead to death. Research also proves that the failure of other vital organs such as kidney, liver, heart, and intestine can also be a result of the cytokine storm, so researchers hypothesize that the death of COVID-19 patients may be reduced if the cytokine storm can be inhibited.

The cytokine storm might also explain why children are "stronger" both from the risk of being infected (which is lower) and even if infected, the chance of fatality is less than that of adults. 

Not only in SARS-CoV-2, in infections caused by the SARS and MERS viruses this also happens, there is no definitive answer in this case, but experts have the hypothesis that the immune system of children under 10 years is imperfect so production of pro- inflammatory cytokines are also lower. source.  

Anti-cytokines Medicine. Before COVID-19, many researchers have tried to find medicines that could inhibit the cytokine storm known as cytokine blockers or anti-cytokines. From the many studies there are several medicines that have been marketed as cytokine blockers such as ustekinumab, infliximab, adalimumab and tocilizumab (these drugs are used by rheumatoid arthritis patients and other auto-immune diseases). Each of these drugs inhibits different types of pro-inflammatory cytokines, there are anti-interleukin [IL] -12 / IL-23, anti-tumor necrosis factor (TNF) and IL-6. A report by Lancet states that patients who take these drugs and are infected and become COVID-19 positive patients have not ended up in the ICU nor have acquired pneumonia. There is no further research whether the drug users above are people who are resistant to COVID-19. source.

 Pneumonia caused by SARS-CoV-2 is characterized by hyper T-immune cell activation and an overproduction of pro-inflammatory cytokines, specifically IL-6. The researchers hypothesized that patients using tocilizumab would be able to control the production of IL-6 cytokines, so they might be more resistant to SARS-CoV-2. The possibility of effective anti-cytokines drugs is currently being investigated. Currently tocilizumab is being studied in China for 188 COVID-19 patients (will be completed on May 3, 2020). Other drugs that work on cytokines such as anti-TNF also receive special attention to be tested on humans immediately. source

 Apart from the result that may show the anti-cytokines medicines to be effectiveness, the price of these drugs is expensive (for example tocilizumab: US $ 20-30 thousand per treatment) and the side effects that can result in patients exposed to bacterial and other viral infections make the above drugs become limited use.

https://www.news-medical.net/health/Estradiol-and-Estrogen-Levels.aspx
https://www.news-medical.net/health/Estradiol-and-Estrogen-Levels.aspx
Germany number of deaths by Age and Gender (as of April 17, 2020)
Germany number of deaths by Age and Gender (as of April 17, 2020)
Estrogen vs. Testosterone. The link between estrogens and cytokines has been widely studied, one of which is estradiol (E2) which is known to inhibit the production of IL-6, a dominant component during the cytokines storm. In addition to IL-6, estrogen especially E2 also inhibits the production of excessive pro-inflammatory cytokines. 

Estrogen levels (especially E2) that are relatively high in women during reproduction to pre-menopause age help the formation of an aggressive immune system (jump-start - innate immune response) and effective. In other words, the response of immune cells when dealing with antigens such as viruses is massive, very fast and precise during innate immune response. 

Estrogen levels of women during reproduction age also control that the response to antigens is proportional during the adaptive immune system works, not excessive that can lead to cytokine storm. The graph below shows women's Estradiol levels drop dramatically when women enter post-menopause but are still higher than men until the age of 70, after that estradiol levels continue to fall with age, but then level of Estrone (E1) increase, replacing the role of E2 in post-menopause women. 

Unlike estradiol, the dominant male hormone testosterone, although it decreases after reaching its peak at the age of 20 years, the decrease is not as drastic as the level of estradiol in women. Long research also explains that high testosterone levels are correlated with a low immune system response, this is evidenced that men with high testosterone levels produce less reactive antibodies when injected with influenza vaccine. Conversely, men with lower testosterone and women respond better and produce more reactive antibodies. source.

Estrogens and Pro-inflammatory Cytokines. Numerous studies have shown a complex relationship between testosterone hormone levels in men and immune cell responses that are inconsistent (sometimes "on", sometimes "off", sometimes too slow, sometimes does not matter). However, this does not happen with the female hormone estrogen. 

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