Non-mumps parotitis associated with influenza A/H3N2: A case series from Southern Italy during the 2024-2025 influenza season.

Parotitis, commonly associated with the mumps virus, can also result from other viral infections. We report a case series of 21 children and preadolescents presenting with mumps-like parotitis in Southern Italy between January and February 2025, all of whom had been vaccinated against mumps. In all cases, mumps virus was not detected by real-time PCR in clinical samples. Alternative etiologies were investigated by testing for a broad panel of pathogens. Viral infections were identified in 16 cases (76.2 %), with influenza A/H3N2 being the most common pathogen (14 cases, 87.5 %), followed by rhinovirus and coronavirus NL63. Of the 14 patients positive for influenza A/H3N2, 10 had received influenza vaccine. Whole genome sequencing of A/H3N2 viruses from three samples was performed, and phylogenetic analysis of the hemagglutinin (HA) gene revealed that they belonged to the A/H3N2 subclade 2a.3a.1 (J.2), clustering with other regional viruses from the 2024 ̶ 2025 season. No unexpected genetic variations were found in target genes that would suggest changes in tissue tropism. Given the emergence of influenza A/H3N2 as a potential etiological agent of non-mumps parotitis, particularly during epidemic periods, enhanced surveillance and comprehensive diagnostic approaches are needed to improve understanding of the epidemiology of non-mumps parotitis.