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Source: COVID-19 Research  May 07, 2020  5 months ago
BREAKING! COVID-19 Research: Study Shows Blood Sugar Could Be Responsible For Triggering Lethal Cytokine Storms In COVID-19
BREAKING! COVID-19 Research: Study Shows Blood Sugar Could Be Responsible For Triggering Lethal Cytokine Storms In COVID-19
Source: COVID-19 Research  May 07, 2020  5 months ago
COVID-19 Research: A new study indicates that glucose metabolism could be playing a key role in the cytokine storm seen in influenza and also SARS-CoV-2 coronavirus infections.


 
So far it has been concluded that many of the patients dying in the COVDI-19 pandemic appear to be harmed more by their own immune system than by the virus itself.
 
The viral infection can trigger a cytokine storm which is a surge in cell-signaling proteins that prompt inflammation and subsequently actually ‘attacks’ the lungs, damaging tissues and potentially resulting in organ failure and death.
 
It has been noted that this phenomenon is not unique to COVID-19; it sometimes occurs in severe influenza as well. Now research findings by Chinese researchers from Wuhan, Zhejiang, Chongqing and also the German Institute of Virology at the University Hospital of Essen, show the metabolic mechanisms that help orchestrate such runaway inflammation.
 
Medical researchers have long known that viral infections can affect human cellular metabolism, the system of biochemical reactions needed to provide energy for everything cells do. In the study, researchers showed that in live mice and human cells, infection with an influenza A virus which is one of two types that typically cause seasonal flu, sets off a cascade of cellular events, or a pathway, that boosts the metabolism of glucose.
 
This cascade of events in turn, triggers the production of an phenomenal amount of cytokines. And blocking a key enzyme involved in the glucose pathway could be one way to prevent a deadly cytokine storm, according to the study, which was published in the journal Science Advances.
https://advances.sciencemag.org/content/6/16/eaaz7086.full
 
Though the study was not focused on the SARS-CoV02 coronavirus, the researchers insists the same mechanism is likely at play in the COVID-19 disease. This correlation could explain why diabetics are at a higher risk of dying from COVID-19.
 
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It has been observed that when a virus infects a cell, it steals resources in order to make copies of itself, infected cells have to boost their metabolism to replenish these resources, and healthy cells must also do so in order to mount an effective immune response.
 
Past research had shown that an influenza infection increases the metabolism of glucose, the sugar molecule that fuels most cellular activities. And in their past research, https://www.jbc.org/content/292/52/21291?ijkey=94ce530527319e59f0543a340ad9491dc45e8408&keytype2=tf_ip secsha the research team of had identified a pathway, involving a signaling protein called interferon regulatory factor 5 (IRF5), in which a flu infection can lead to a cytokine storm.
 
The researchers revealed in the new research, at a detailed molecular level, how a glucose metabolism pathway activated by flu infection leads to an out-of-control immune response.
 
During such a viral infection, high levels of glucose in the blood cause an enzyme called O-linked β-N-acetylglucosamine transferase (OGT) to bind to, and chemically modify, IRF5 in a process known as glycosylation. This step enables another chemical modification, called ubiquitination that leads to a cytokine inflammatory response.
 
The medical researchers infected mice with influenza A and then administered glucosamine, a sugar that kicks off this glucose metabolism pathway. They showed that doing so increased the production of cytokines.
 
Subsequently, the researchers genetically engineered animal models (mice0 that lacked the gene that enables OGT production. These animal models did not develop an over-the-top cytokine response when exposed to glucosamine.
 
The researchers in the final sate of the study analyzed blood collected from flu patients and healthy individuals in Wuhan, China, between 2018 and 2019.
 
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The team found that the flu-infected individuals’ blood had higher glucose levels and correspondingly higher levels of immune system signaling molecules than that of the healthy individuals. That findings further supports the idea that glucose metabolism plays a role in flu infection.
 
The research results suggest that interfering with this pathway could be one way to prevent the cytokine storm seen in flu and other viral infections. Such an intervention would need to be done carefully, however, to avoid shutting off the body’s ability to fight the virus altogether.
 
Study co-author Dr Mengji Lu, a Professor at University Hospital Essen’s Institute of Virology in Germany told Thailand Medical News, “It could be relevant to interfere with glucose metabolism using chemical inhibitors and to modulate the cytokine production. But it needs to be said that energy metabolism is essential for our immune cells to fight any virus. It may be important to combine antiviral treatment and metabolic inhibitors, hence suppressing the virus and reducing the overshooting immune reaction at the same time.”
 
Dr Lu said that a same process of runaway cytokine production has been observed in COVID-19. However there are no specific drugs that target the SARS-CoV-2 virus that causes the disease, so interference with energy metabolism alone may result in breakdown of our immune defense and does not provide a benefit.
 
Many other medical experts confirm that the research findings paper does a nice job of proposing and validating one mechanism by which metabolic changes can feed forward the inflammatory responses. Previous studies had shown more broadly that glucose metabolism plays a role in the response to flu infection. However this is the only study that details what is going on at the molecular level and how interfering with this process could prevent uncontrolled inflammation.
 
The research results also confirm what Dr Haitao Wen, now an assistant Professor of Immunology at Ohio State University, and his colleagues found in a 2018 study of the same metabolic pathway using a different RNA virus. https://www.ncbi.nlm.nih.gov/pubmed/30543776
 
Another 2019 study  by other researchers also came to similar conclusions. All studies show that the OGT enzyme involved in this pathway is required to initiate the host’s stress response to a viral infection. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31001-0
 
Dr  Wen added, “The initial point of this stress response is to build up an antipathogen immune response and try to fight against virus but if the inflammatory response keeps going, it will cause collateral damage.”
 
When asked that given the role of glucose in the pathway, could an individual’s diet have an effect on his or her response to a viral infection, Dr Wen said that at this moment, it’s too early to make a conclusion a special diet can fight against virus infection.
 
However what medical researchers do know is that people with type 2 diabetes are more susceptible to severe flu infections. But that risk is not because they have higher glucose levels in their blood. The real reason, Dr Wen says, is that they cannot use glucose effectively and thus cannot initiate a proper antiviral response.
 
The researchers ultimately hope that by interfering with this glucose metabolism pathway, they might be able to stave off the deadly cytokine storms seen in severe cases of flu or COVID-19.
 
However Dr Lu cautions that studies have yet to be done on humans and there is no data of patients demonstrating the effect of interference with energy metabolism, hence it is premature to make a conclusion about the potential clinical application.
 
For the latest COVID-19 Research, keep logging to Thailand Medical News
 
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