Serotonin reduction in post-acute sequelae of viral infection

The study titled “Serotonin Reduction in Post-Acute Sequelae of Viral Infection” explores the mechanisms and consequences of serotonin reduction in individuals with Post-Acute Sequelae of COVID-19 (PASC), also known as Long COVID.

The main findings of the study are as follows:

  1. Association of PASC with Serotonin Reduction: The study identifies a significant global health challenge posed by PASC, characterized by persistent cardiorespiratory, neurocognitive, gastrointestinal, and musculoskeletal symptoms. It links serotonin reduction to PASC, suggesting that viral infection and the associated interferon-driven inflammation contribute to this reduction through multiple mechanisms. These include diminished absorption of tryptophan (a precursor to serotonin), platelet hyperactivation and thrombocytopenia affecting serotonin storage, and enhanced serotonin turnover due to increased activity of monoamine oxidase (MAO) enzymes.
  2. Investigation of Mechanisms: Through a combination of human cohort studies, animal models, and organoid cultures, the study demonstrates that viral RNA and downstream interferon responses cause a decrease in serotonin. This reduction is driven by diminished uptake of tryptophan in the gastrointestinal tract, reduced storage in platelets, and enhanced turnover by serotonin-metabolizing enzymes.
  3. Impact on Cognitive Function: Peripheral serotonin deficiency was found to impair the activity of the vagus nerve, leading to hippocampal dysfunction and memory loss. In mouse models, acute viral infections and poly(I:C)-treated mice showed cognitive impairments, which were alleviated by treatments that restored serotonin levels or stimulated vagal signaling. This suggests a direct link between serotonin reduction and neurocognitive symptoms observed in Long COVID.
  4. Broader Implications: The study highlights the profound implications of persistent viral reservoirs, such as sustained type I interferon response, which might be a causative factor in developing PASC-associated symptoms. It also underscores the potential broad impact of viral infections on nutrient uptake and metabolism, beyond serotonin, including other important metabolites derived from tryptophan.

Overall, the study provides a comprehensive analysis of how viral inflammation, particularly in the context of COVID-19, can lead to a reduction in serotonin levels and contribute to the symptoms observed in Long COVID. It offers insights into potential therapeutic interventions targeting serotonin pathways to alleviate these symptoms.

Read More: https://www.cell.com/cell/fulltext/S0092-8674(23)01034-6

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