Introduction:
This opinion article attempts to connect knowledge about post-COVID syndrome (PCS) gained in neuropsychiatry and immunology. It discusses some misunderstandings about PCS in light of the interplay between the serotonergic system and the kynurenine pathway (KP). From a new perspective, potential biomarkers for further research and therapeutic targets are identified.
Due to the severity and extent of PCS, researchers are urgently searching for its causes and treatments. For neurocognitive and autonomic nervous system problems such as present in PCS, it is common to encounter dysregulated neurotransmitter systems. Among the neurotransmitters, serotonin plays a special role in the immune system and in regulating inflammatory responses by central and peripheral mechanisms (1–5). Serotonin—also known as 5-hydroxytryptamine (5-HT)—is a neurotransmitter with a stimulating effect that influences memory, mood, self-confidence, sleep, emotion, orgasm and eating (6–9).
Serotonin not only binds to serotonergic receptors on neurons, but also to receptors on immune cells (3, 5, 10, 11). Many studies indicate that serotonin and its receptors, especially 5-HT3 receptors (one of the serotonin receptors), are involved in the pathogenesis of chronic inflammatory conditions (5, 10, 11). Therapeutic applications of 5-HT3 receptor antagonists for instance have been reported in rheumatoid arthritis (5, 11, 12). An essential amino acid in the serotonin system and also in the KP is tryptophan, a precursor of both serotonin and kynurenine (see Figure 1) and part of a regular diet (14). The KP is a pathway creating an important energy factor and is modulated in conditions as infection and stress (1, 5). Kynurenine regulates the balance between two types of thymus cells (T-cells): regulatory T-cells (Treg-cells), and subsets of T helper 17 cells (Th17 cells) that produce cytokines and have a signaling function (15).
In this opinion article I address the question whether disruptions in the serotonin- and kynurenine pathway metabolism lead to new biomarkers and treatment in PCS.
Source: Rus CP. Disruptions in serotonin- and kynurenine pathway metabolism in post-COVID: biomarkers and treatment. Front Neurol. 2025 Feb 13;16:1532383. doi: 10.3389/fneur.2025.1532383. PMID: 40027165; PMCID: PMC11869386. https://pmc.ncbi.nlm.nih.gov/articles/PMC11869386/ (Full text)