Many of the people dying in the COVID-19 pandemic are harmed by their own immune system rather than by the virus itself.  The infection triggers a cytokine storm – a surge in cell signalling proteins that prompt inflammation that hits the lungs, attacking tissues and potentially resulting in organ failure and death.

But this phenomenon is not unique to COVID-19.  It sometimes occurs in severe influenza.  A study reported in the Scientific American Journal shows one of the metabolic mechanisms that may help to orchestrate such runaway inflammation. 

It has been known for a while that viral infections can affect human cellular metabolism, that is the system of biochemical reactions needed to provide energy for everything that cells do. 

Research has found that in live mice and human cells, infection with influenza A virus sets off a chain of cellular events that boosts the metabolism of glucose.  This action in turn triggers the production of an avalanche of cytokines.  It is hypothesised that blocking a key enzyme involved in the glucose pathway could be one way to prevent a deadly cytokine storm. 

Although this research was not focused on COVID-19, the same mechanism is likely.  This could explain why people with diabetes are at a higher risk of dying from the virus. 

Paul Thomas, an immunologist at St Jude Children’s Research Hospital in Memphis suggested that when a virus infects a cell it steals the resources from that cell in order to make copies of itself.  Infected cells have to boost their metabolism to replenish these resources and healthy cells must also do this in order to mount an effective immune response. 

Prior research has shown that influenza infection increases the metabolism of glucose.  This is the sugar molecule that fuels most cellular activities.  In previous work the authors of this paper identified a pathway involving a signalling protein called interferon regulatory 5, which caused in infections a cytokine storm.  In their latest study, the team revealed how a glucose metabolism pathway activated by flu infection leads to an out of control immune response.  During such an infection high levels of glucose in the blood leads to a biochemical pathway which leads to a cytokine inflammatory response.

The researchers proved in mice infected with influenza A that when they administered glucosamine, a sugar that kicks off the glucose metabolism pathway, there was an increased production of cytokines.  They also showed that genetically engineered mice that were unable to glycosylate did not develop an over the top cytokine response when exposed to glucosamine. 

Finally, the researchers analysed blood collected from flu patients and healthy individuals in Wuhan, China between 2018 and 2019.  They found that in the flu-infected subjects’ there were higher glucose levels – and corresponding higher levels of immune system signalling molecules – than in healthy patients.

These results further support the idea that glucose metabolism plays a role in flu infection.  These findings suggest that interfering with this pathway could be one way to prevent the cytokine storm seen in flu and other viral infections.

However, one would have to do this very carefully to avoid shutting off the body’s ability to fight the virus altogether and the energy metabolism which is also essential for immune cells to fight a virus.  This leads to the hypothesis that combining antiviral treatment and metabolic inhibitors which suppress the virus and reduce the over-shooting immune reaction at the same time may be the way to conquer COVID-19 infection. 

Similar processes of runaway cytokine production have been observed in COVID-19 but at present there are no specific drugs that target the SARS-CoV-2 virus that causes the disease.  If we interfere with just the energy metabolism, this may result in a breakdown of our immune defence and provide no benefit. 

Given the role of glucose in the pathway, could a person’s diet have an effect on his or her response to a viral infection?

At this moment in time it is probably too early to make a judgement on whether a special diet can fight against viral infection.

However, we know that people with type 2 diabetes are more susceptible to severe flu infections.  This risk is not because they have higher glucose levels in their blood, it is probably because they cannot use the glucose which they have effectively and thus cannot initiate a proper antiviral response. 

This is a very interesting article which is a basis for future research and trials in order to hopefully prevent the disastrous effects of COVID-19 infection.

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