Abstract
Background: Mumps virus remains an important cause of outbreaks in vaccinated populations despite widespread use of measles–mumps–rubella/varicella (MMR/V) vaccines. Early in 2026, an increase in mumps cases was identified within the Johns Hopkins Health System (JHHS), coinciding with statewide reported cases in the state of Maryland. Methods: Molecular testing was implemented for case confirmation, and positive specimens underwent whole-genome sequencing. Epidemiologic and clinical data were abstracted from medical records. Phylogenetic analysis was performed using complete and partial genomes. Results: Eight patients with laboratory-confirmed mumps infection were identified. The median age was 31 years. Parotitis was the predominant presentation, followed by epididymo-orchitis. Whole-genome sequencing demonstrated that all viruses belonged to mumps virus genotype C and formed a tightly clustered monophyletic lineage with 99.95% nucleotide similarity, consistent with local transmission. Sequences were genetically distinct from genotype G strains reportedly associated with outbreaks in the United States. Comparison with the Jeryl Lynn vaccine strains (genotype A) showed ~7.5% nucleotide divergence. Amino acid analysis of the hemagglutinin-neuraminidase protein identified multiple substitutions in antigenic regions. Conclusions: A genotype C mumps virus cluster was identified during the 2026 Maryland outbreak. Findings are consistent with the introduction and local transmission of an uncommonly reported genotype, supporting the need for widespread molecular diagnostics, and highlighting the value of whole-genome sequencing for outbreak characterization.