# The Clinical Utility of Serum Biomarkers in the Differentiation and Prognostic Assessment of Viral Meningitis

**Authors:** Georgiana Enache-Leonte, Andrei Vâță, Maria Ioana Onofrei, Mihnea Eudoxiu Hurmuzache, Gabriela Rusu Zota, Dan Trofin, Ioana Alina Harja-Alexa, Mihaela Cătălina Luca

PMC · DOI: 10.3390/pathogens15020234 · Pathogens · 2026-02-20

## TL;DR

This study explores how blood markers can help distinguish between viral and bacterial meningitis and predict patient outcomes.

## Contribution

The study identifies serum biomarkers like SII and GPx3 as potential predictors for meningitis etiology and prognosis.

## Key findings

- VM patients had lower NLR, PLR, and SII, and higher GPx3 compared to BM patients.
- SII and GPx3 were significant predictors of meningitis etiology in multivariate analysis.
- The SII was the strongest predictor of mortality in viral meningitis.

## Abstract

Background and Objectives: Viral meningitis presents significant diagnostic challenges. The aim of this study was to identify predictive factors for meningitis etiology and clinical outcomes. Methods: This prospective, single center, comparative study enrolled patients meeting clinical, biological, and microbiological criteria for bacterial (BM) or viral (VM) meningitis. Serum inflammatory markers, namely the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), were quantified. In addition, the concentrations of oxidative stress biomarkers, glutathione peroxidase 3 (GPx3) and copper/zinc superoxide dismutase (Cu/Zn SOD), were also determined. Spearman correlation and logistic regression were used to evaluate associations between biomarkers and etiology, while receiver operating characteristic (ROC) curves assessed outcome correlations. Results: VM patients showed a significantly lower NLR (p = 0.007), PLR (p = 0.010), and SII (p = 0.016), with higher GPx3 (p < 0.0001) levels compared with BM patients. Cu/Zn SOD showed no significant difference (p = 0.442) between groups. Multivariate logistic regression identified the SII (OR = 1.015; 95% CI = 1.004–1.026) and GPx3 (OR = 0.847; 95% CI = 0.740–0.970) as etiology predictors. The SII was the strongest predictor of mortality in VM (AUC = 0.833). Conclusions: Serum markers of inflammation, including the systemic immune–inflammation index, along with antioxidant indicators such as GPx3, may serve as valuable additional tools for predicting meningitis etiology and forecasting patient outcomes.

## Linked entities

- **Proteins:** GPX3 (glutathione peroxidase 3), CSD2 (copper/zinc superoxide dismutase 2)
- **Diseases:** viral meningitis (MONDO:0007015), bacterial meningitis (MONDO:0006670)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, GPX3 (glutathione peroxidase 3) [NCBI Gene 2878] {aka GPx-P, GSHPx-3, GSHPx-P}, CAT (catalase) [NCBI Gene 847], SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}
- **Diseases:** multiple organ dysfunction (MESH:D009102), autoimmune disorders (MESH:D001327), acute meningitis (MESH:D000208), fever (MESH:D005334), seizures (MESH:D012640), NLR (MESH:D015467), critically ill (MESH:D016638), injury (MESH:D014947), systemic infections (MESH:D012141), liver disease (MESH:D008107), conditions (MESH:D020763), headache (MESH:D006261), SII (MESH:D007249), West Nile virus infection (MESH:D014901), cancer (MESH:D009369), SIRS (MESH:D018746), lung cancer (MESH:D008175), neurotoxic damage (MESH:D020258), Meningitis (MESH:D008580), neurological complications (MESH:D002493), chronic renal disease (MESH:D051436), neuroinflammatory (MESH:D000090862), neck stiffness (MESH:D006258), heart failure (MESH:D006333), Neisseria meningitides A, C, Y and W135 (MESH:D008581), Bacterial infections (MESH:D001424), systemic (MESH:D015619), liver disorders (MESH:D017093), mycobacterial or fungal meningitis (MESH:D016921), VM (MESH:D008587), brain abscess (MESH:D001922), acute herpes zoster meningitis (MESH:D006562), CNS infections (MESH:D002494), septic shock (MESH:D012772), sepsis (MESH:D018805), chronic (MESH:D002908), Infectious Diseases (MESH:D003141), cognitive impairment (MESH:D003072), Coma (MESH:D003128), neurological impairment (MESH:D009422), tissue injury (MESH:D017695), BMS (MESH:D016920), Viral infections (MESH:D014777), atherosclerotic cardiovascular disease (MESH:D050197), death (MESH:D003643), COVID-19 (MESH:D000086382), immune (MESH:D007154), cerebral hemorrhage or infarction (MESH:D002544), Encephalitis (MESH:D004660), enteroviral infections (MESH:D007239), neutrophilic pleocytosis (MESH:D007964), aseptic meningitis (MESH:D008582)
- **Chemicals:** copper (MESH:D003300), hydroxyl radicals (MESH:D017665), chloride (MESH:D002712), nitric oxide (MESH:D009569), zinc (MESH:D015032), vitamin E (MESH:D014810), nitrogen (MESH:D009584), lactate (MESH:D019344), omega-3 fatty acids (MESH:D015525), GSH (MESH:D005978), peroxynitrite (MESH:D030421), OH (MESH:C031356), lipid (MESH:D008055), N-acetylcysteine (MESH:D000111), ROS (MESH:D017382), glucose (MESH:D005947), creatinine (MESH:D003404), curcumin (MESH:D003474), melatonin (MESH:D008550), O2- (MESH:D013481), H2O2 (MESH:D006861), urea (MESH:D014508), selenium (MESH:D012643), GSSG (MESH:D019803)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Human immunodeficiency virus 1 (no rank) [taxon 11676], Streptococcus pneumoniae (species) [taxon 1313], Human alphaherpesvirus 3 (Varicella-zoster virus, no rank) [taxon 10335], Escherichia coli K1 (strain) [taxon 1392869], Enterovirus (genus) [taxon 12059], West Nile virus (no rank) [taxon 11082], Streptococcus sp. 'group B' (species) [taxon 1319], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943159/full.md

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Source: https://tomesphere.com/paper/PMC12943159