Medical Research

New Explanation for Long Covid

Kristen Sparrow • October 17, 2023

The new theory behind some of the symptoms of Long Covid is that the virus stays in the gut. This article from the New York Times explains that the residual virus tends up  depleting seratonin levels.

The following quote is important.  Peripheral serotonin deficiency impairs cognition via reduced vagal signaling

I went to a conference on Neuromodulation about 18 months ago and there was a presentation about using Vagal stimulation in the hospital on Covid Patients.  Now there seems to be a good rationale for doing this, as well as for treating with acupuncture to try to improve vagal signalling.

Wong, A. C., Devason, A. S., Umana, I. C., Cox, T. O., Dohnalová, L., Litichevskiy, L., Perla, J., Lundgren, P., Etwebi, Z., Izzo, L. T., Kim, J., Tetlak, M., Descamps, H. C., Park, S. L., Wisser, S., McKnight, A. D., Pardy, R. D., Kim, J., Blank, N., . . . Levy, M. (2023). Serotonin reduction in post-acute sequelae of viral infection. Cell.


  • Long COVID is associated with reduced circulating serotonin levels

  • Serotonin depletion is driven by viral RNA-induced type I interferons (IFNs)

  • IFNs reduce serotonin through diminished tryptophan uptake and hypercoagulability

  • w


Post-acute sequelae of COVID-19 (PASC, “Long COVID”) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

Graphical abstract