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.
Matits et al. (Sat,) studied this question.