(Medford MA, October 15, 2023) – PolyBio Research Foundation is excited that a paper partly supported via our LongCovid Research Consortium was published today in the journal Cell. The paper – titled “Serotonin reduction in post-acute sequelae of viral infection” – was authored by Dr. Maayan Levy and team at the University of Pennsylvania. The study identifies mechanisms by which SARS-CoV-2 persistence in the gut may contribute to chronic inflammation, hypercoagulability, and autonomic dysfunction in Long COVID.
More specifically the team found that Long COVID was associated with serotonin reduction in blood and persistent SARS-CoV-2 RNA in stool. To explore these findings they performed a series of experiments in tissue models and mice. They discovered that persistent viral RNA and type I interferon-driven inflammation can reduce serotonin via three mechanisms: 1) reduced intestinal uptake of tryptophan, the biosynthetic precursor of seratonin 2) reduced counts of platelets, which carry serotonin in the circulation and 3) enhanced enzymatic turnover of serotonin. Serotonin reduction might – in turn – alter activity of the vagus nerve, contributing to autonomic symptoms.
“How do [persistent] viral infections result in serotonin reduction? wrote Dr. Maayan Levy about the study on Twitter/X. “We found that type 1 interferon signaling was required, which is interesting light of recent reports suggesting that viral persistence and sustained elevation of interferons are characteristic of Long COVID.”
The findings may extend to persistent RNA viruses beyond SARS-CoV-2. “With SARS-CoV-2 gut reservoirs increasingly identified in Long COVID and enterovirus gut reservoir connected to ME/CFS, the possibility that common symptoms could in part result from persistent viral RNA type 1 interferon-driven reduction in plasma serotonin is intriguing” says Amy Proal, PhD, President of PolyBio Research Foundation.
Overall the study weaves together several prominent lines of evidence on the potential drivers of Long COVID — the ongoing presence of viral material, blood clotting and chronic inflammation — and offers up possible targets for clinical trials that can test treatments in humans. These include tryptophan supplementation or vagus nerve stimulation.