Prevalence and Molecular Profiling of Merkel Cell Polyomavirus in Patients With Monkeypox Virus Infection

ABSTRACT Mpox, caused by Monkeypox virus (MPXV), is associated with mucosal involvement and immune modulation that may influence viral coinfections. Merkel Cell Polyomavirus (MCPyV), a ubiquitous virus capable of lifelong persistence, was investigated in 66 Mpox patients enrolled at Lazzaro Spallanzani National Institute for Infectious Diseases (Rome, Italy; 2022–2025). Oropharyngeal and anal swabs collected during acute Mpox and, at 9‐month follow‐up, were analyzed by quantitative PCR, sequencing, transcript, and microRNA assays. MCPyV DNA was detected in 23/66 (34.8%) individuals, with higher prevalence and load in anal (31.8%, 2.1 × 10 3 copies/mL) than in oropharyngeal swabs (24.4%, 1.3 × 10 2 copies/mL; p < 0.001). MCPyV persisted in 4/10 (40%) oropharyngeal samples at follow‐up. No viral integration was observed, and full‐length Large Tumor Antigen was amplified in all samples. Transcript analysis revealed early and late genes; viral microRNAs were found in 3/10 (30%) oropharyngeal and 5/14 (35.7%) anal acute‐phase swabs, and persisted in 3/4 (75%) MCPyV‐positive oropharyngeal samples at follow‐up. Among the 12 MCPyV‐positive people living with human immunodeficiency virus (HIV), MCPyV load was lower in oropharyngeal but higher in anal swabs compared to MCPyV/MPXV cases. This study provides the first evidence of MCPyV detection in Mpox‐positive individuals and supports further investigation of its clinical relevance in coinfection settings.