Serotonin reduction in post-acute sequelae of viral infection - Article Summary

serotonin-reduction-in-post-acute-sequelae-of-viral-infection-article-summary.md

TLDR Version

• 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
• Peripheral serotonin deficiency impairs cognition via reduced vagal signaling

Graphical Abstract

Level 1 Drilldown

Main hypotheses formulated to explain the etiology of Post-acute sequelae of COVID-19 (PASC, "Long COVID")

• viral persistence,
• chronic inflammation,
• hypercoagulability, and
• autonomic dysfunction

The link between them

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

This impacts

• serotonin storage; and
• enhanced Monoamine oxidase (MAO) mediated serotonin turnover.

Peripheral serotonin reduction, in turn,

• impedes the activity of the vagus nerve and
• thereby impairs hippocampal responses and memory.

Possible targets for clinical interventions aimed at the prevention and treatment of PASC

Serotonin levels can be restored and memory impairment reversed by

• precursor supplementation or
• SSRI treatment
• Targeting serotonin signaling for the prevention or treatment of neurocognitive manifestations.

Relationships to other conditions

• Viral
  • Reduced serotonin levels in dengue virus infection, which is the trigger of another post-viral syndrome
• Non-viral
  • systemic lupus erythematosus or
  • multiple sclerosis

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