GFAP as a Marker of Neuroinflammation in Patients with COVID-19: A Comparative Analysis with Alzheimer’s and Parkinson’s Disease

Abstract Background: Persistent neurocognitive symptoms following COVID-19 may stem from sustained neuroinflammation. Glial fibrillary acidic protein (GFAP) is a blood marker of astroglial activation; how it aligns COVID-19 with neurodegenerative diseases remains unclear. Methods: We compared plasma GFAP and a focused panel (fractalkine/CX3CL1, MDC/CCL22, sCD40L, IP-10/CXCL10, VEGFA) across patients hospitalized with COVID-19 who later developed post-COVID neurological symptoms (n=36), Alzheimer’s disease (AD, n=40), Parkinson’s disease (PD, n=44), and controls (n=30). Assays used xMAP Luminex (panel) and ELISA (GFAP). Non-parametric statistics (Kruskal–Wallis; Mann–Whitney, α=0.01) and multivariate analyses (PCA, LDA) were performed on log-transformed, standardized data in R 4.5.1. Results: GFAP was elevated versus controls in COVID-19 (median 308 pg/mL) and PD (475 pg/mL) and modestly increased in AD (250 pg/mL) compared with controls (194 pg/mL). COVID-19 showed a distinct inflammatory signature with markedly reduced fractalkine and MDC, and increased IP-10, while AD/PD exhibited higher sCD40L and VEGFA. GFAP did not differ between COVID-19 and AD, positioning astroglial activation as a shared axis. PCA/LDA placed COVID-19 between controls and AD/PD, indicating partial convergence with neurodegeneration yet a unique acute-inflammation profile. Conclusions: Blood GFAP aligns COVID-19 with AD/PD on astrocytic activation, whereas chemokine and platelet-activation markers distinguish COVID-19 from chronic neurodegeneration. These findings support composite biomarker panels for stratifying post-COVID neuroinflammation. Competing Interest Statement The authors have declared no competing interest. Funding Statement Supported by Saint Petersburg State University, project ID: 103963512 Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approved by the Ethics Committee of City Hospital No. 40, protocol 215 (April 20, 2022); written informed consent obtained. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors