tetano
Editor, Senior Moderator
Brain Behav Immun
. 2026 Jul 18:106918.
doi: 10.1016/j.bbi.2026.106918. Online ahead of print.
Cerebral gray matter volumes in long-term post-COVID patients are associated with peripheral kynurenine pathway metabolites and the severity of depressive symptoms
Lynn Matits[SUP] 1 [/SUP], Jana Schellenberg[SUP] 2 [/SUP], Alexander Rau[SUP] 3 [/SUP], Iris-Tatjana Kolassa[SUP] 4 [/SUP], Dietrich Rothenbacher[SUP] 5 [/SUP], Raphael S Peter[SUP] 5 [/SUP], Winfried V Kern[SUP] 6 [/SUP], Meinrad Beer[SUP] 7 [/SUP], Benjamin Bender[SUP] 8 [/SUP], Marianne Schell[SUP] 9 [/SUP], Georg Grön[SUP] 10 [/SUP], Daniel Alexander Bizjak[SUP] 2 [/SUP], Johannes Kirsten[SUP] 2 [/SUP], Jürgen M Steinacker[SUP] 11 [/SUP], Vivien Richter[SUP] 8 [/SUP], Nico Sollmann[SUP] 12 [/SUP]
Affiliations
Background: Structural brain changes and immune-metabolic alterations are widely reported in post-COVID condition (PCC), particularly among patients with depressive symptoms. Alterations in gray matter volume (GMV) and dysregulation of the peripheral kynurenine pathway have each been described independently in PCC; however, potential interactions remain unclear. This observational case-control study investigated associations between GMV and peripheral kynurenine-pathway metabolites in patients with PCC compared to unimpaired individuals who recovered after COVID-19.
Methods: The analysis is based on a sub-cohort from a multicentre, population-based study of individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between October 2020 and April 2021. We compared 43 patients with PCC (age: M = 47.63 (SD = 13.01), 74.4% female) to 27 age- and sex-matched fully recovered controls (age: M = 47.44 (SD = 10.39), 77.8% female) on average 156 weeks after SARS-CoV-2 infection. GMV was assessed using isotropic T1-weighted magnetic resonance imaging (MRI) data (normalized to total intracranial volume, age, and sex). We analyzed the relation of normalized regional GMV to serum kynurenine-pathway metabolites (kynurenine, kynurenic acid, quinolinic acid, kynurenic/quinolinic acid ratio). Additionally, in patients with PCC, GMV and kynurenine-pathway metabolites were tested for correlations with the severity of depressive symptoms.
Results: No significant group-level differences in GMV were observed. Clinical case status moderated the association between the peripheral kynurenic acid/quinolinic acid ratio and GMV of the right cingulate gyrus and right parietal lobe. Post-hoc analyses showed a positive association in PCC. Furthermore, within the PCC group, 60.5% showed depressive symptoms according to the Patient Health Questionnaire-9, and larger bilateral hippocampal volumes were significantly associated with greater depressive symptom severity. None of the kynurenine pathway metabolites were significantly associated with depressive symptom severity.
Conclusion: Our findings may indicate that the peripheral kynurenine metabolism is associated with GMV in PCC, suggesting the presence of facilitated immune-brain interactions. The association between higher hippocampal GMV and depressive symptom severity in PCC-associated depression points to a distinct neurobiological mechanism.
Keywords: Central nervous system; Gray matter volume; Kynurenic acid; Kynurenine; Quinolinic acid; SARS-CoV-2.
. 2026 Jul 18:106918.
doi: 10.1016/j.bbi.2026.106918. Online ahead of print.
Cerebral gray matter volumes in long-term post-COVID patients are associated with peripheral kynurenine pathway metabolites and the severity of depressive symptoms
Lynn Matits[SUP] 1 [/SUP], Jana Schellenberg[SUP] 2 [/SUP], Alexander Rau[SUP] 3 [/SUP], Iris-Tatjana Kolassa[SUP] 4 [/SUP], Dietrich Rothenbacher[SUP] 5 [/SUP], Raphael S Peter[SUP] 5 [/SUP], Winfried V Kern[SUP] 6 [/SUP], Meinrad Beer[SUP] 7 [/SUP], Benjamin Bender[SUP] 8 [/SUP], Marianne Schell[SUP] 9 [/SUP], Georg Grön[SUP] 10 [/SUP], Daniel Alexander Bizjak[SUP] 2 [/SUP], Johannes Kirsten[SUP] 2 [/SUP], Jürgen M Steinacker[SUP] 11 [/SUP], Vivien Richter[SUP] 8 [/SUP], Nico Sollmann[SUP] 12 [/SUP]
Affiliations
- PMID: 42471068
- DOI: 10.1016/j.bbi.2026.106918
Background: Structural brain changes and immune-metabolic alterations are widely reported in post-COVID condition (PCC), particularly among patients with depressive symptoms. Alterations in gray matter volume (GMV) and dysregulation of the peripheral kynurenine pathway have each been described independently in PCC; however, potential interactions remain unclear. This observational case-control study investigated associations between GMV and peripheral kynurenine-pathway metabolites in patients with PCC compared to unimpaired individuals who recovered after COVID-19.
Methods: The analysis is based on a sub-cohort from a multicentre, population-based study of individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between October 2020 and April 2021. We compared 43 patients with PCC (age: M = 47.63 (SD = 13.01), 74.4% female) to 27 age- and sex-matched fully recovered controls (age: M = 47.44 (SD = 10.39), 77.8% female) on average 156 weeks after SARS-CoV-2 infection. GMV was assessed using isotropic T1-weighted magnetic resonance imaging (MRI) data (normalized to total intracranial volume, age, and sex). We analyzed the relation of normalized regional GMV to serum kynurenine-pathway metabolites (kynurenine, kynurenic acid, quinolinic acid, kynurenic/quinolinic acid ratio). Additionally, in patients with PCC, GMV and kynurenine-pathway metabolites were tested for correlations with the severity of depressive symptoms.
Results: No significant group-level differences in GMV were observed. Clinical case status moderated the association between the peripheral kynurenic acid/quinolinic acid ratio and GMV of the right cingulate gyrus and right parietal lobe. Post-hoc analyses showed a positive association in PCC. Furthermore, within the PCC group, 60.5% showed depressive symptoms according to the Patient Health Questionnaire-9, and larger bilateral hippocampal volumes were significantly associated with greater depressive symptom severity. None of the kynurenine pathway metabolites were significantly associated with depressive symptom severity.
Conclusion: Our findings may indicate that the peripheral kynurenine metabolism is associated with GMV in PCC, suggesting the presence of facilitated immune-brain interactions. The association between higher hippocampal GMV and depressive symptom severity in PCC-associated depression points to a distinct neurobiological mechanism.
Keywords: Central nervous system; Gray matter volume; Kynurenic acid; Kynurenine; Quinolinic acid; SARS-CoV-2.