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.