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Proteomic Analysis of Cerebrospinal Fluid from Severe COVID-19 Patients Reveals Prognostic Biomarkers Associated with Disease Outcome

Proteomics Clin Appl. 2026 Mar;20(2):e70042. doi: 10.1002/prca.70042.

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) has highlighted significant neurological complications in severe cases. Cerebrospinal fluid (CSF) proteomics could reveal biomarkers related to clinical outcome among critically ill patients.

EXPERIMENTAL DESIGN: We performed high-resolution proteomic analyses of CSF samples from 29 intensive care unit (ICU) patients with severe COVID-19 and 19 controls. Differentially expressed proteins and associated pathways were identified through bioinformatic and statistical analyses.

RESULTS: Proteomic analysis identified 488 significantly altered proteins between COVID-19 patients and controls. Proteins linked to coagulation, inflammation, and blood-brain barrier dysfunction (e.g., SERPINC1, KNG1, PLG) were elevated in patients who survived ICU admission. Conversely, proteins associated with metabolic disruption, cellular stress, and neuroinflammation (e.g., FABP3, PDIA4) were upregulated in non-survivors. Pathway enrichment analyses confirmed involvement of immune activation, inflammatory responses, and coagulation cascades.

CONCLUSIONS AND CLINICAL RELEVANCE: CSF proteomics in severe COVID-19 patients reveals potential biomarkers predictive of patient outcomes. These findings support the involvement of systemic inflammation and blood-brain barrier disruption in COVID-19 pathophysiology, suggesting novel targets for personalized intervention strategies.

PMID:41830303 | DOI:10.1002/prca.70042

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