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

Choroid Plexus Enlargement in Post-COVID-19 Syndrome Is Linked to Serum-Induced Cytokine Secretion in Human Hippocampal Progenitors | Research Square Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Choroid Plexus Enlargement in Post-COVID-19 Syndrome Is Linked to Serum-Induced Cytokine Secretion in Human Hippocampal Progenitors Daniel Martins, Nicole Mariani, Julia Schubert, Brandi Eiff, Silvia Rota, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8981267/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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. Biological sciences/Cell biology Health sciences/Diseases/Psychiatric disorders Post-COVID-19 syndrome choroid plexus neuroinflammation immune–brain interface cerebrospinal fluid astrocytes magnetic resonance imaging human neural progenitor cells Figures Figure 1 Figure 2 Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Supplementary Files Supplementary.pdf Supplementary Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information

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