Cerebrospinal Fluid Proteomic Profiling Reveals Proteins Associated with Neuroinflammatory Response in COVID-19 Patients

The COVID-19 pandemic has highlighted the diverse clinical manifestations of SARS-CoV-2 infection, including neurological complications. This study investigates cerebrospinal fluid (CSF) proteomic profiles to identify proteins associated with neuroinflammatory processes in COVID-19. CSF samples from 11 critically ill patients and 5 COVID-19-negative controls were analyzed using high-resolution liquid chromatography-tandem mass spectrometry. A total of 203 proteins were identified, of which 76 exhibited differential expression peptides (DEPs). Proteins involved in coagulation (fibrinogen alpha and beta chains, prothrombin) and immune responses (complement cascade components, immunoglobulin heavy constant gamma, kappa, and lambda subunits) were significantly upregulated in COVID-19 patients. In contrast, proteins involved in antioxidant defense (e.g., superoxide dismutase) and neural maintenance (e.g., neural cell adhesion molecule 1, Neuronal cell adhesion molecule) were significantly downregulated. Functional annotation revealed enriched pathways associated with hemostasis, immune regulation, and neuroinflammatory responses. Protein-protein interaction analysis highlighted interactions among complement and coagulation cascade components, underscoring their roles in inflammation and potential thrombotic complications. These findings suggest that SARS-CoV-2 infection induces significant alterations in the CSF proteome, reflecting neuroinflammatory and oxidative stress mechanisms. Identifying these proteins and their association with diverse pathophysiological mechanisms provides insights into the neurological impact of COVID-19 and may serve as therapeutic targets and potential biomarkers. Further studies are needed to validate these findings and explore their clinical implications in post-COVID-19 neurological syndromes.