Abstract
INTRODUCTION: Monkeypox (Mpox) has reemerged globally, with thousands of confirmed cases reported in China. However, limited data exist on the genomic variations and transmission patterns of monkeypox virus (MPXV) in southwestern China. METHODS: Clinical samples from Mpox cases and sewage samples from wastewater treatment plants were collected from Sichuan Province for whole-genome sequencing and MPXV analysis. RESULTS: In the second half of 2023, 96 clinical samples from Mpox patients were collected, yielding 58 full-length viral genomes. All sequenced viruses belonged to the Western African clade (IIb), comprising three C.1 and fifty-five C.1.1 sequences. This study determined that Mpox cases in Sichuan originated from both importation and subsequent local transmission, with evidence of at least six distinct transmission clusters. Additionally, 26 sewage samples were collected, and 3 complete MPXV genomes were constructed. Analysis of viral genomes from sewage samples demonstrated a 95% concordance in high-frequency mutation sites with those observed in clinical cases, suggesting that sewage surveillance effectively captures diagnosed cases and serves as a robust complement to conventional monitoring. The integration of newly sequenced genomes with published data revealed an increased mutation rate in MPXV, along with fluctuating patterns of expansion and contraction of the effective viral population size. CONCLUSION: This study provides preliminary insights into MPXV transmission dynamics and genomic evolution in Sichuan and demonstrates the utility of sewage monitoring in tracking viral diversity.