Controlling inflammation in COVID-19 patients may lessen severity of the novel coronavirus
UC researcher part of a team of scientists exploring COVID-19’s cytokine storm
A University of Cincinnati researcher is trying to understand what occurs when COVID-19 invades the lungs causing the body’s immune cells go into overdrive.
The UC researcher is part of a team of scientists studying the body’s response when viral particles carrying COVID-19 enter the lungs, and the body — specifically its immune system — and react in a catastrophic way. Immune cells flood and attack the lungs that they should be protecting, in what scientists call a “cytokine storm.”
These cytokines, or small proteins, are the immune system’s “messengers.” Normally some ask for more immune activity, some request less.
“There is tremendous inflammation that occurs in the lungs,” explains Steve Davidson, PhD, assistant professor of anesthesiology in the UC College of Medicine. “Part of what we wanted to know was is this lung inflammation partly due to a neuroimmune interaction? Do neurons innervating the lungs contribute to this robust inflammatory reaction to COVID-19? We needed to figure out whether compounds released by the immune response targeted receptors on the sensory neurons innervating the lung.”
Davidson was recruited by Theodore Price, PhD, professor of neuroscience at the University of Texas at Dallas and leader of the research team, because of Davidson’s expertise in recovering a cluster of neurons in the human spinal cord known as the dorsal root ganglia. These primary sensory neurons relay information to the central nervous system from all parts of the body including the lungs and play a role in the body’s immune response.
Price, along with 13 scientists in his lab and Davidson, published a study in the journal Brain, Behavior, and Immunity, that identified interactions between immune cells and nerves in the lungs that cause a COVID-19 patient’s condition to worsen. Price says the team’s research shows that drugs used in treating rheumatoid arthritis to tamp down inflammation might be part of a therapy to help COVID-19 patients in the future. None of the drugs have undergone clinical trials in COVID-19 patients, but they may offer a pathway to limiting the body’s immune response.
Price says nervous system inflammation means the body’s immune system and nervous system start to interact in what becomes a vicious cycle. “That cycle can lead to rapid and runaway inflammation and that seems to happen in some of these patients,” explains Price.
Davidson says the team examined a COVID-19 patient database from China that included fluid taken from the lungs and allowed gene signature and cell and cytokine responses to be measured and determined. Researchers then compared genes in COVID-19 patients to what is evident in the sensory neurons from healthy individuals.
They developed a computational method to look at how immune cells and nervous system cells in COVID-19 patients might interact and then merged these two profiles together to examine the results, says Davidson.
“What we saw was a pretty unique signature,” explains Price.
Neurotransmitter receptors undergo a striking increase in the response to a stimulus in immune cells in the lungs, says Price. The immune cells appear to communicate through a neurotransmitter known as glutamate that is released by activated nerve endings in the lung. There are antagonists to block this occurrence.
Data suggests one way to tamp down the inflammatory response in the lungs is by mitigating the activity of a specific cytokine, known as CCL2. That pathway could be disrupted with drugs that target rheumatoid arthritis, says Price. That approach failed when it was tested against influenza and bird flu.
But Price says it doesn’t mean it won’t work in COVID-19 patients and should be considered for additional study by researchers.
“I think most people, even in biomedical research, don’t really appreciate the extent that the nervous system interacts with every single organ in your body,” says Price. “Having a disease and the way the immune system and nervous system interact are really important for the outcome of the disease. If the nervous system and immune system interaction goes in the wrong direction, it can make you really sick really quickly.
“The better we understand this and all these kinds of diseases, the better position we will be in knowing when patients go from being really sick to needing a ventilator,” says Price.
Other co-authors all from the University of Texas at Dallas include Pradipta R. Ray, PhD; Andi Wangzhou; Nizar Ghneim; Muhammad S. Yousuf, PhD; Candler Paige; Diana Tavares-Ferreira PhD; Juliet M. Mwirigi; Stephanie Shiers, PhD; Ishwarya Sankaranarayanan; Amelia J. McFarland, PhD; Sanjay V. Neerukonda; Gregory Dussor, PhD; and Michael D. Burton, PhD.
Funding for this study was supported by National Institutes of Health grants NS065926 and NS115441. Price disclosed he is a co-founder and board member of 4E Therapeutics.
Featured photo of Steve Davidson, PhD, by Colleen Kelley/UC Creative + Brand.
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