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

Category	Detail
Condition	Human metapneumovirus (hMPV) infection causing respiratory illness
Key Mechanisms	Infection of upper and lower respiratory tract epithelial cells; induces type 1 interferon immune response; incomplete long-lasting immunity leading to reinfections
Target Population	Children (universally infected by age 5), adults including those with immunosuppression and chronic comorbidities
Care Setting	Outpatient and inpatient settings including intensive care units

hMPV is a single serotype virus with 2 major subgroups (A and B) and 5 sublineages, showing continuous genetic evolution.
hMPV causes 2% to 7% of symptomatic respiratory infections in children and can cause severe pneumonia in adults, especially with risk factors.
Long-lasting immunity to hMPV is incomplete, allowing reinfections throughout life; cellular and humoral immunity are important for viral clearance.

Consider hMPV in differential diagnosis of respiratory infections in children and adults, especially with bronchiolitis or pneumonia.
Use molecular diagnostic methods to detect hMPV given its similarity to RSV and other respiratory viruses.

Supportive care remains the mainstay of treatment; no specific antiviral therapy is currently approved.
Monitor patients with risk factors such as immunosuppression, congestive heart failure, and severe COPD closely due to higher risk of severe disease.

Observe for progression to severe respiratory disease requiring hospitalization, ICU admission, or mechanical ventilation in high-risk adults.
Monitor immune status in immunocompromised patients as lymphopenia and cytotoxic therapy increase severity risk.

Severe disease risk factors include profound immunosuppression (20%), congestive heart failure (25%), and severe chronic obstructive pulmonary disease (20%).
Reinfections are common due to waning immunity and viral genetic diversity.

Children universally infected by age 5; adults with chronic comorbidities and immunosuppression at higher risk for severe disease

No licensed antiviral treatments; vaccine development focuses on humoral responses targeting the conserved F protein to provide protection.

Include hMPV in respiratory viral panels for accurate diagnosis in symptomatic patients.
Recognize and monitor high-risk adult populations for severe outcomes.
Support vaccine development efforts targeting the F protein to enhance protective immunity.
Provide supportive care tailored to severity and comorbid conditions.

Clinical Scorecard: A Comprehensive Review of Insights and Knowledge Gaps in the 25 Years Following the Identification of Human Metapneumovirus as a Human Pathogen