An internationally circulating chikungunya virus lineage with distinct mutational signatures was associated with the 2025 outbreak in China

A large-scale chikungunya outbreak was reported in southern China in 2025. We systematically characterized the clinical, virological, and molecular epidemiological features of the outbreak in Guangdong Province. A total of 208 laboratory-confirmed patients were included, from whom 164 complete chikungunya virus genomes were obtained. The outbreak was characterized by a short, concentrated transmission period, with no clear evidence of sustained, multi-wave transmission. Patients ranged in age from 1 to 90 years, with most cases occurring among individuals aged 20–70 years. Fever, arthralgia, and rash were the predominant clinical manifestations, and fever and arthralgia frequently occurred concurrently. Increasing age was independently associated with a lower hazard of hospital discharge. Compared with historically reported cases, the frequencies of fever and arthralgia were similar, whereas rash was more common and myalgia, fatigue, headache, nausea, and vomiting were less frequent. All outbreak-associated viruses were assigned to Clade 2 of the East/Central/South African genotype and closely matched the globally documented Rank 4 mutational profile. These findings suggest that the outbreak was more likely caused by the introduction and subsequent expansion of an established international lineage than by the local emergence of a novel variant. Several key amino acid substitutions were predicted to influence envelope protein stability, receptor engagement, antibody recognition, and adaptation to Aedes albopictus. It is necessary to continue clinical and genomic surveillance, strengthen vector control measures, and establish a cross-regional early warning system.