Prognostic value of NLR, SII, PCT, and PLR in sepsis and septic shock: a systematic review and meta-analysis

Importance Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Accessible inflammatory biomarkers may improve early risk stratification for mortality or short-term adverse prognosis in septic patients. Objective To systematically evaluate the prognostic associations of four routinely available inflammatory biomarkers (NLR, PLR, PCT, SII) with mortality or short-term adverse prognosis in patients with sepsis and septic shock. Three PROSPERO protocol deviations (CRD420251035190) were documented: the research question, biomarker set, and effect-measure synthesis all changed from the registered protocol. Methods Ten cohort studies involving 2,412 patients were included. Random-effects meta-analyses were performed, with OR and HR analyzed separately, and continuous and categorical effects synthesized separately. Results Two studies reported PCT with endpoint-specific estimates (Wang 2024 mortality OR = 1.957 [1.243−3.081]; Li Liang 2024 composite OR = 2.827 [1.694–4.718]; not pooled per §2.5). SII showed a significant HR-based association [pooled HR = 1.4112 (1.2568–1.5846); P < 0.0001; I 2 = 0.0%; k = 2]. Continuous NLR showed minimal heterogeneity in the primary OR-based synthesis [pooled OR = 1.0146 per unit (1.0098–1.0195); P < 0.001; I 2 = 0.0%; k = 2; Ren 2022 + Song 2025]; the exploratory analysis including the Wang 2024-recalc value yielded OR = 0.9660 [0.9121–1.0230]; I 2 = 96.3%; P = 0.237. PLR was not significant [pooled OR = 1.7491 (0.9597–3.1877); P = 0.0679; I 2 = 95.4%]. Conclusion The present meta-analysis does not support strong clinical recommendations. The evidence is hypothesis-generating and should be interpreted with caution due to three major PROSPERO protocol deviations, moderate-to-high risk of bias, small sample sizes for PCT and SII, and substantial heterogeneity for PLR and exploratory NLR. These biomarkers should be interpreted as components of multidimensional risk assessment, not stand-alone prognostic tools. Systematic Review Registration PROSPERO ID CRD420251035190.