IntroductionAn excessive systemic pro-inflammatory state increases the risk of severe disease and mortality in patients with coronavirus disease 2019 (COVID-19). However, there is uncertainty regarding whether specific biomarkers of inflammation can enhance risk stratification in this group. We conducted a systematic review and meta-analysis to investigate an emerging biomarker of systemic inflammation derived from routine hematological parameters, the systemic inflammation index (SII), in COVID-19 patients with different disease severity and survival status.MethodsA systematic literature search was conducted in PubMed, Web of Science, and Scopus, between the 1stof December 2019 and the 15thof March 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation, respectively (PROSPERO registration number: CRD42023420517).ResultsIn 39 studies, patients with a severe disease or non-survivor status had significantly higher SII values on admission compared to patients with a non-severe disease or survivor status (standard mean difference (SMD)=0.91, 95% CI 0.75 to 1.06, p<0.001; moderate certainty of evidence). The SII was also significantly associated with the risk of severe disease or death in 10 studies reporting odds ratios (1.007, 95% CI 1.001 to 1.014, p=0.032; very low certainty of evidence) and in six studies reporting hazard ratios (1.99, 95% CI 1.01 to 3.92, p=0.047; very low certainty of evidence). Pooled sensitivity, specificity, and area under the curve for severe disease or mortality were 0.71 (95% CI 0.67 to 0.75), 0.71 (95% CI 0.64 to 0.77), and 0.77 (95% CI 0.73 to 0.80), respectively. In meta-regression, significant correlations were observed between the SMD and albumin, lactate dehydrogenase, creatinine, and D-dimer.DiscussionOur systematic review and meta-analysis has shown that the SII on admission is significantly associated with severe disease and mortality in patients with COVID-19. Therefore, this inflammatory biomarker derived from routine haematological parameters can be helpful for early risk stratification in this group.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023420517.