Clinical and Laboratory Predictors of Severe Leptospirosis, Intensive Care Unit Admission, and Mortality: A Systematic Review of Prognostic Factors

Abstract

Background: Leptospirosis is a zoonotic infection that may range from a mild febrile illness to severe multisystem disease with renal, pulmonary, hepatic, haematological, and haemodynamic complications. Early recognition of patients at risk of severe outcomes is important for timely clinical management. This systematic review synthesised evidence on clinical and laboratory predictors associated with severe leptospirosis, intensive care unit admission, and mortality. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidance and was registered in PROSPERO. Electronic databases, including PubMed/MEDLINE, Scopus, Web of Science, Embase, CINAHL, Google Scholar, and Semantic Scholar, were searched from database inception to the final search date. Eligible studies included human studies that evaluated clinical, laboratory, radiological, demographic, or biomarker predictors of severe leptospirosis and reported severity-related outcomes. Data were extracted using a standardised form and synthesised narratively because of heterogeneity in study designs, severity definitions, predictor variables, and outcome measures. Results: Twenty-six studies involving more than 42,000 participants met the inclusion criteria. The most consistently reported predictors of severe disease and adverse outcomes were oliguria, acute kidney injury, elevated serum creatinine, elevated urea, thrombocytopenia, leukocytosis, hypotension, pulmonary involvement, jaundice, hyperbilirubinemia, advanced age, and delayed initiation of antibiotic therapy. Renal dysfunction and pulmonary complications were the most recurrent predictors across the included studies. Emerging biomarkers, including C-reactive protein, protein carbonyl, and selected immunological markers, showed potential prognostic value but were supported by limited validation. Conclusion: Severe leptospirosis is associated with identifiable clinical and laboratory abnormalities, particularly renal, pulmonary, haematological, hepatic, and haemodynamic markers. Routine clinical assessment and basic laboratory investigations may support early risk stratification and guide timely escalation of care in patients with suspected leptospirosis.