Human metapneumovirus: an underdiagnosed public health threat

Human metapneumovirus (hMPV), a negative-sense RNA virus in the Pneumoviridae family, has emerged as a major yet under-recognized cause of acute respiratory infections worldwide. Since its identification in 2001, hMPV has shown steady genetic evolution into genotypes A and B, with newer sublineages such as A2.2.1, A2.2.2, and B2 currently detected across continents. A recent global rise in hMPV detections, detailed in reports from China, Europe, and the USA, likely reflects both expanded testing and the re-establishment of seasonal circulation following the COVID-19 pandemic. Co-infections with respiratory viruses, including RSV and influenza, contribute to severe clinical outcomes and hospital burden. Multiplex RT-PCR remains the most sensitive and widely used diagnostic method for detection of hMPV, outperforming conventional PCR approaches, while metagenomic sequencing and CRISPR-based assays are primarily research tools. Diagnostic sensitivity also varies with sample source, and access to advanced technologies remains globally uneven. Despite its growing clinical impact, no approved antiviral is available. Promising candidates, including monoclonal antibodies against the fusion protein, siRNA therapies, and mRNA-based vaccines, are in the early stages of development. This review encompasses recent evidence on hMPV epidemiology, molecular evolution, diagnostic approaches, and therapeutic and vaccine development, underscoring a need for sustained surveillance, equitable diagnostic capacity, and proactive vaccine research more effectively addressing a largely overlooked respiratory pathogen.