Choroid Plexus Enlargement in Post-COVID-19 Syndrome Is Linked to Serum-Induced Cytokine Secretion in Human Hippocampal Progenitors

Background : Post-COVID-19 syndrome (PCS) is characterised by persistent cognitive, affective, and somatic symptoms that extend months beyond acute SARS-CoV-2 infection, frequently in the absence of overt systemic inflammation. While immune dysregulation is increasingly implicated, the mechanisms linking peripheral immune alterations to enduring brain-related symptoms remain poorly understood. The choroid plexus (CP), a specialised blood–cerebrospinal fluid barrier and neuroimmune interface, is well positioned to mediate such immune–brain communication. Methods : In this case–control study, we combined high-resolution structural MRI with peripheral immunophenotyping and a functional human neural progenitor model to investigate the neuroimmune relevance of CP morphology in PCS. Twenty individuals with PCS following mild acute COVID-19 and twenty recovered controls underwent MRI for manual CP segmentation, serum cytokine profiling, and serum exposure assays using human hippocampal progenitor cells. Results : Individuals with PCS exhibited significantly enlarged CP volume compared with recovered controls, independent of intracranial volume. CP enlargement showed minimal association with circulating cytokine concentrations, indicating limited correspondence with contemporaneous peripheral inflammatory markers. In contrast, CP volume was robustly associated with serum-induced immune and astrocytic responses in vitro, including reduced IL-8 secretion and altered astrocytic marker expression (GFAP and AQP4), while no associations were observed with neuronal differentiation markers. Conclusions : These findings demonstrate a dissociation between static peripheral cytokine levels and functional brain-relevant immune effects, and suggest that CP enlargement preferentially indexes brain-proximal neuroimmune signalling capacity rather than peripheral inflammatory load alone. By integrating neuroimaging with human cellular assays, this study positions the choroid plexus as a structural marker of persistent neuroimmune dysregulation in PCS and highlights immune–barrier interfaces as critical targets for understanding post-infectious brain symptoms.