Pathogen spectrum identified by targeted nanopore sequencing and exploratory analysis of hematological biomarkers in suspected intracranial infections

Background: Intracranial infections are severe, life-threatening conditions often caused by diverse pathogens. Targeted nanopore sequencing (TNPseq) offers rapid and accurate pathogen identification, addressing the limitations of traditional diagnostic methods. Besides the pathogen types, factors like inflammation levels also affect treatment outcomes. Thus, we combined TNPseq with clinical indicators to characterize pathogen-specific host-response heterogeneity and optimize clinical stratification in infected patients. Methods: This retrospective study included 255 patients with suspected intracranial infections, among whom 39 with complete clinical and hematological data were analyzed. Pathogen detection was conducted using TNPseq, and the consistency of pathogen distributions between the full and screened cohorts was evaluated. The diagnostic performance of C-reactive protein (CRP), neutrophil ratio (NR), and procalcitonin (PCT) was assessed via logistic regression and receiver operating characteristic (ROC) curve analysis. Mediation analysis was used to explore the relationship between CRP, NR, and the length of hospital stay (LOS). Results: , with similar distributions in both cohorts. Among biomarkers, CRP had the highest diagnostic accuracy, followed by PCT and NR. Additionally, NR and CRP were closely related to the LOS. Mediation analysis suggested that NR fully mediated the effect of CRP on LOS, with higher NR levels associated with longer hospital stays. Conclusion: TNPseq effectively identifies a broad range of pathogens in intracranial infections. CRP and NR serve as critical indicators of inflammatory burden and host-response heterogeneity, aiding in risk stratification and personalized management when integrated with TNPseq.