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A new approach to averting inflammation caused by COVID-19

by University of Minnesota

Controlling the body's inflammatory response to SARS-CoV-2 will likely be as important as antiviral therapies or a potential vaccine

FAB RESEARCH COMMENT:

Leading researchers explain here why and how 'resolvins' and other regulatory substances derived from long-chain omega-3 fatty acids (EPA and DHA) offer a promising new way to control the excessive inflammation responsible for the most severe and life-threatening forms of illness that the new coronavirus can cause in vulnerable individuals.

Resolvins are made naturally within the body from both EPA and DHA, and are already known to play an active and critical role in reducing and resolving inflammation. Specially synthesised versions have already been trialled in other conditions involving excessive inflammation. 

Other mediators derived from EPA help to reduce both excessive inflammation and blood-clotting - the latter being another complication associated with severe COVID-19 illness.

The long-chain omega-3 fatty acids (EPA and DHA, found in fish and seafood) act as raw materials for a huge array of 'lipid mediators' that help regulate immune function, blood flow, hormonal balance and many other functions.

Very broadly, mediators derived from omega-3 EPA and DHA (including eicosanoids and resolvins) have anti-anflammatory actions, and improve blood flow, while eicosanoids derived from the main long-chain omega-6 (arachidonic acid) tend to promote inflammation and enhance blood clotting.

This explains why an appropriate omega-3/6 balance is so important for health. But typical modern, western-type diets are seriously imbalanced, as they are very low in long-chain omega-3 fats (found in fish and seafood), but high in omega-6 (found in meat, eggs, dairy products and all vegetable oils).   

Importantly, the 'underlying health conditions' associated with vulnerability to more severe forms of COVID-19 - including obesity, Type 2 diabetes and cardiovascular disease - are themselves associated with persistent inflammation.   Chronic inflammation also raises the risks for many developmental and mental health conditions - most notably depression, but also ADHD and related conditions.

All of these 'non-communicable disorders' are of course also strongly linked with the consumption of modern, western-type diets rich in omega-6, and relatively lacking in omega-3 fats.

These new findings not only offer promise for the management of severe COVID-19 illness. They also reinforce a huge body of existing evidence showing that increasing omega-3 intakes, and therefore improving omega-3/6 balance, could also improve immune system (and cardiovascular) health more generally, and reduce the prevalence and severity of the many chronic physical and mental health conditions in which excessive inflammation is now implicated.

For more details on this new research article, which is open-access, see:

12 May 2020 - MedicalXpress  

Severe COVID-19 illness can result in excessive inflammation throughout the body, including the lungs, heart and brain. University of Minnesota Twin Cities student Molly Gilligan recently published an article in the journal
Cancer & Metastasis Reviews that studied the human body's robust inflammatory response to the SARS-CoV-2 virus, which is now recognized as a hallmark symptom.

According to the publication, controlling the body's inflammatory response to SARS-CoV-2 will likely be as important as antiviral therapies or a potential vaccine. Individual mediators—called cytokines—cause inflammation in response to tissue injury or infection. Mediators are a substance or structure that mediates a specific response in a bodily tissue.

Rather than blocking cytokines,
medical staff could turn off virus-induced inflammation by broadly activating the body's natural inflammation-clearing activities.

"We are now recognizing the importance of controlling this robust inflammatory response in COVID-19 infection in order to reduce associated
organ damage and mortality," said Gilligan, a student at the Medical School. "Finding new ways to dampen the body's inflammatory response to COVID-19 will likely be as important as finding effective antiviral therapies to control COVID-19 infection and reduce life-threatening organ damage."

"Moreover, these compounds have been found to be non-toxic and non-immunosuppressive in ongoing clinical trials for other inflammatory diseases, making them even more promising candidates for rapid clinical translation," said Gilligan.

The research found that:
  • one hallmark of SARS-CoV-2 infection is a cytokine storm, which is a drastic increase in immune cell production of cytokines;
  • SARS-CoV-2 causes unchecked inflammation that can cause extensive organ damage, such as lung failure;
  • current therapeutic strategies in COVID-19 focus on inhibiting a single pro-inflammatory cytokine rather than broadly inhibiting the body's inflammatory response;
  • lipid mediators derived from omega-3 fatty acids serve as the body's natural "stop" signals to inflammation.
  • Increasing levels of these lipid mediators in the body could be a new therapeutic approach to preventing life-threatening inflammation caused by SARS-CoV-2.

"What is exciting for us is that these lipid mediators that 'turn off,' or resolve, inflammation are already in clinical trials for other inflammation-driven diseases, such as eye disease, periodontal disease and pain," said Dipak Panigrahy, an assistant professor of pathology in Beth Israel Deaconess Medical Center. "The mediators can quickly be applied to turn off inflammation in COVID-19 patients."