Human Metapneumovirus: An Underestimated Cause of Severe Respiratory Infection

Abstract Since its identification in 2001, human metapneumovirus (hMPV) has been recognized as an important cause of acute respiratory tract infection in all age groups. Although infection is often mild in healthy adults, hMPV can cause severe lower respiratory tract disease, including pneumonia, in young children, older adults, individuals with chronic diseases and immunocompromising conditions, and residents of long-term care facilities. Accumulating evidence demonstrates that hMPV contributes substantially to hospitalization, intensive care unit admission, and mortality in these high-risk populations. Globally, hMPV circulates seasonally, most commonly in late winter and spring, contributing to both community- and healthcare-associated respiratory infections; however, the COVID-19 pandemic disrupted established epidemiology, resulting in shifts in epidemic timing, off-season resurgences, genotype replacement, and increased overlap with other respiratory viruses, while also providing insights into viral interference and multivirus cocirculation. Clinical manifestations of hMPV overlap with other respiratory viruses, including influenza virus or SARS-CoV-2, and selective diagnostic practices contribute to under-recognition and under-testing. Although no specific antiviral therapies or licensed vaccines are currently available, identification of hMPV has important implications for diagnostic accuracy, prognosis, antimicrobial stewardship, and infection prevention, particularly in hospital and long-term care settings. This review summarizes current evidence on the virology, epidemiology, post–COVID-19 trends, clinical manifestations, outcomes, diagnosis, and prevention of hMPV, with a particular focus on adults and other high-risk populations. We also review the current landscape of hMPV vaccine development and its potential implications for clinical practice and public health.