Review: Knowledge Gained and Gaps in Understanding in the 25 Years Since Human Metapneumovirus Was First Identified as a Cause of Human Disease

Abstract

Human metapneumovirus (hMPV) is a nonsegmented, single-stranded, negative-sense RNA virus belonging to the Pneumoviridae family. It was first identified in 2001 in the nasopharyngeal secretions of 28 Dutch children with bronchiolitis collected over a 20-year period. hMPV exhibited paramyxovirus-like morphology with many genetic similarities to respiratory syncytial virus. hMPV has 1 serotype with 2 major subgroups (A and B) and 5 sublineages (A1, A2a, A2b, B1, and B2). In the wake of its discovery, a wealth of observational research has demonstrated global circulation of hMPV causing a wide spectrum of clinical disease. It accounts for 2% to 7% of all symptomatic respiratory infections in children who are universally infected by age 5 years. However, long-lasting immunity to hMPV is incomplete, and reinfections occur throughout life. With increasing age, the impact of hMPV is greater. Adult patients with hMPV infection may develop pneumonia, resulting in hospitalization and severe outcomes, such as intensive care unit admission or mechanical ventilation. Risk factors for severe hMPV are still being defined but include profound immunosuppression (20%), congestive heart failure (25%), and severe chronic obstructive pulmonary disease (20%). In this supplement, several studies from diverse geographic and clinical locations explore the pathogenesis, epidemiology, and clinical profile of hMPV as compared with respiratory syncytial virus and/or influenza and examine the impact of risk factors for severe disease, including age and chronic comorbid conditions. These data are needed to provide the basis for understanding who might benefit from future hMPV vaccines.

Keywords: clinical profile of hMPV infections; epidemiology and global circulation; human metapneumovirus; pathogenesis and immune responses to hMPV; risk for severe disease adults.

Figure 1.

Human metapneumovirus and respiratory syncytial virus genome. Reprinted from Feigin and Cherry's Textbook of Pediatric Infectious Diseases with permission from JV Williams.

Figure 2.

Microneutralization titers after human metapneumovirus infection in adults. Adapted from a figure in the study by Falsey et al [28].

Figure 3.

NREVSS reporting of hMPV infection: 2020–2023. Abbreviations: hMPV, human metapneumovirus; NREVSS, National Respiratory and Enteric Virus Surveillance System.

Figure 4.

PATH RSV vaccine and mAb snapshot: February 2025. Abbreviations: mAb, monoclonal antibody; RSV, respiratory syncytial virus.