Mpox in Europe, 2022-2026: A Scoping Review of Viral Clades, Host Determinants of Severity and Antiviral Therapy.

The 2022-2024 mpox outbreak in Europe was dominated by MPXV Clade IIb and generally mild, but recent Clade I/Ib detections and early local transmission have changed preparedness needs. We performed a PRISMA-ScR scoping review of European mpox evidence from 2022 to 2026, supplemented by global and African data where regional evidence was sparse, covering clades, host determinants of severe disease, and antiviral efficacy and resistance, and ranking the evidence gaps. European Clade IIb surveillance showed very low mortality (10 deaths among 22,662 cases; case fatality 0.04%), contrasting with 3-11% estimates for Clade I/Ib in affected African settings, although comparisons are confounded by age, health-system access and comorbidity. Severe European disease was driven mainly by immune compromise: non-HIV immunosuppression, uncontrolled HIV and CD4 counts < 200 cells/µL were the most consistent markers, while women were a small minority of cases, with higher hospitalisation risk, especially in pregnancy. Tecovirimat failed to improve outcomes in four randomised trials, F13L-associated resistance was reported in advanced HIV, and its European mpox use was subsequently restricted. The evidence base is strongest for mild Clade IIb infection in immunocompetent adults and weakest for the groups most likely to need treatment. Preparedness should prioritise harmonised genomic surveillance, severity-stratified cohort data and adaptive therapeutic trials enrolling immunocompromised, paediatric, pregnant and older patients.