Clinical factors associated with mortality in ebola virus disease: a systematic review and meta-analysis

BACKGROUND: Ebola virus disease (EVD) remains a major global public health threat because of its high case fatality rate and recurrent outbreaks, particularly in sub-Saharan Africa. Despite advances in supportive care and targeted therapies, mortality remains substantial and varies widely across epidemics and healthcare settings. A robust quantitative synthesis is therefore needed to estimate overall mortality and identify clinical determinants associated with death among patients with EVD. METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA 2020 guidelines. PubMed, Google Scholar, and Index Medicus Africa were searched from inception to November 10, 2025. Observational studies reporting mortality among patients with EVD were included. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist. A random-effects meta-analysis using restricted maximum likelihood estimation was performed to calculate pooled mortality and odds ratios (ORs) for factors associated with death. Heterogeneity was assessed using the I² statistic, and subgroup analyses were conducted by epidemic period, region, sample size, and age group. Publication bias was evaluated using funnel plots and Egger's and Begg's tests. RESULTS: Eleven studies involving 16,413 patients with EVD were included. Reported case fatality proportions ranged from 34% to 79%. The pooled mortality was 54% (95% CI: 45-63), with very high heterogeneity (I² = 98.2%). Mortality was higher during the West African epidemic (2014-2016) than during more recent Central African outbreaks (2018-2020). Pediatric mortality appeared lower than adult mortality, although confidence intervals overlapped. Hemorrhagic manifestations were strongly associated with death, whereas age was not independently associated with mortality in pooled analyses. No significant publication bias was detected. CONCLUSIONS: EVD remains associated with high mortality, although improvements in outcomes are evident in more recent outbreaks. Hemorrhagic manifestations represent a key clinical determinant of death. These findings highlight the importance of early access to care, high-quality supportive management, and sustained implementation of effective therapeutic strategies to further reduce EVD-related mortality, particularly in resource-limited settings.