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

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.