The effect of inflammation, SARS-CoV-2 infection, age and mental health on serotonin, and kynurenine and catecholamine pathway metabolites.

Background: A high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery.
Methods: The cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression.
Results: In the SIMMUN cohort, the inflammatory marker neopterin (β = 0.47 [95% CI: 0.34-0.61]), SARS-CoV-2-positivity (0.42 [0.16-0.68]), mental stress (0.18 [0.055-0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (-0.38 [-0.68 to -0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: -0.22 [-0.38 to -0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: -0.15 [-0.26 to -0.036]). Serotonin (0.76 [0.34-1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28-0.99]) were higher during recovery than in acute SARS-CoV-2 infection.
Conclusion: SARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19.
Competing Interests: Declaration of Competing Interest Katharina Hüfner has received research grants from Austria Wirtschaftsservice (AWS) and the Science Fund of the Land Tirol as well as lecturer’s honoraria from Forum Medizinische Fortbildung (FOMF), the Hospital of Schwaz and the Austrian Society for Biological Psychiatry related to the topic of COVID-19. Piotr Tymoszuk owns the Data Science as a Service Tirol enterprise and works a free-lance data scientist and biostatistician. He has received an honorarium for statistical data analysis, bioinformatic and scientific writing services. Bernhard Holzner has intellectual property rights to the CHES software tool used for questionnaire data collection. Jens Lehmann reports consultancy for Evaluation Software Development GmbH, the software company developing CHES. All other authors report no conflicts of interest related to the current manuscript.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)