Global complications among patients with mpox: a systematic review and meta-analysis

Background: Despite increasing global attention, significant knowledge gaps remain regarding the incidence of adverse outcomes associated with mpox. To support the development of World Health Organization (WHO) mpox guidelines, this systematic review and meta-analysis evaluated the incidence of complications among patients with mpox. Methods: We searched Medline, Embase, CENTRAL, CINAHL, Global Health, medRxiv, bioRxiv, and SSRN from database inception to December 20, 2025, for studies reporting complications in patients with laboratory-confirmed mpox of all ages. Paired reviewers independently screened studies, extracted data, and assessed risk of bias. We conducted proportional meta-analyses using the inverse variance method fixed-effect model with the Freeman-Tukey double arcsine transformation and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We classified mpox as severe or non-severe based on the need for hospitalization or the study's criteria. We registered the protocol with PROSPERO (CRD42024595685). Findings: Of 4566 records, 170 studies with 127,564 patients (mean age 6.9-43.0 years) proved eligible. Among patients with non-severe mpox, serious complications were rare. Mortality, intensive care unit admission, sepsis, pneumonia, encephalitis, epiglottitis, myocarditis, gastrointestinal bleeding, and pleural effusion all occurred in ≤0.5% of patients (moderate to high certainty evidence). Urinary retention, mechanical ventilation, urethritis, gastroenteritis, and keratitis occurred in 0.7%-1.8% (moderate to high certainty evidence). Severe pain, abscess, tonsillitis, conjunctivitis, and cellulitis occurred in 2.2%-3.7% of patients (moderate certainty evidence) and hospitalization occurred in 4.4% (low certainty evidence). Patients who were vaccinated had a lower hospitalization rate than those who were unvaccinated. Patients in low- and middle-income countries (LMICs) had a higher rate of pneumonia (2.21% versus 0.02%) than those in high-income countries (HICs). In patients with severe mpox, complication rates were substantially higher. All-cause mortality, abscess, sepsis, tonsillitis, keratitis, and mechanical ventilation occurred in 2.5%-5.5% of patients (moderate certainty evidence). Acute kidney injury, pleural effusion, respiratory failure, and conjunctivitis occurred in 1.4%-2.0% (moderate to high certainty evidence). Patients with severe mpox in LMICs had a higher mortality (3.18% versus <0.01%) than those in HICs. Interpretation: Non-severe mpox is associated with low complication rates and very low mortality, while severe disease carries substantial risks of life-threatening complications and death. These findings provide baseline risk estimates for both patients with severe and non-severe mpox, emphasize the importance of early risk stratification in clinical management, and highlight the need for tailored approaches based on disease severity. The data also reveal health inequities in mpox care between HICs and LMICs, underscoring the urgent need for increased resources in LMICs. Funding: World Health Organization.