What is known about human metapneumovirus, particularly in young children, older adults, and individuals with compromised immune systems?

Human Metapneumovirus: Clinical Overview

Pathogen Characteristics and Epidemiology

Human metapneumovirus (HMPV) is a paramyxovirus discovered in 2001 that causes acute respiratory tract infections across all age groups, with particular severity in infants, young children, older adults, and immunocompromised individuals. 1, 2

• HMPV accounts for 5-10% of hospitalizations in children with acute respiratory tract infections 3, 4
• Nearly all children are infected by age 5, with reinfections common throughout life due to transient immunity 5
• Retrospective serologic studies demonstrate HMPV antibodies in humans dating back more than 50 years before its formal discovery 5
• The virus demonstrates significant genetic variability and antigenic diversity, complicating vaccine development 6

Clinical Manifestations

Pediatric Presentations

In children, HMPV most commonly presents with bronchiolitis and pneumonia, with symptoms indistinguishable from respiratory syncytial virus (RSV). 1, 3

• Upper respiratory symptoms include rhinorrhea, nasal congestion, cough, and fever 7, 8
• Additional pediatric symptoms include fatigue, expectoration, diarrhea, headache, dyspnea, cyanosis, malaise, restlessness, poor feeding, and reduced activity 8
• Severe cases can progress to respiratory failure unresponsive to conventional oxygen therapy, septic shock, metabolic acidosis, and coagulation dysfunction 8
• HMPV has been associated with exacerbations of asthma, croup, and concomitant otitis media 1
• Most children present with mild to moderate symptoms 1

Adult Presentations

In adults, HMPV causes upper respiratory tract infections that often mimic influenza and can exacerbate chronic obstructive pulmonary disease (COPD) and asthma. 1, 6

• Patients with chronic cardiac or pulmonary diseases face elevated risk of severe disease 8
• The presence of cardiopulmonary comorbidities substantially increases mortality risk 8

Immunocompromised Patients

HMPV causes severe lower respiratory tract disease in immunocompromised patients, particularly hematopoietic stem cell transplant (HSCT) recipients, with mortality rates of 10-30%. 8, 9

• Risk factors for severe disease include early post-transplant status, higher corticosteroid exposure, neutropenia, and lymphopenia 9
• Asymptomatic and prolonged viral shedding occurs frequently in immunocompromised populations, complicating infection control 8, 9
• Nosocomial outbreaks can occur given the estimated incubation period of 2.6 days and high rates of asymptomatic shedding 9

Laboratory Findings

Laboratory abnormalities include leukocytosis, leukopenia, neutrophilia, lymphopenia, and elevated inflammatory markers. 6

Diagnostic Approach

Nucleic acid amplification tests (NAATs), particularly reverse transcriptase PCR, are the preferred diagnostic modality due to fastidious growth in cell culture. 1, 3, 4

• Respiratory secretions or nasopharyngeal swabs placed in appropriate viral transport medium are the specimens of choice 1
• Immunofluorescent assays are available but less commonly used 1
• NAATs are now widely available in commercial respiratory panels 1
• Viral culture may take extended periods and is not recommended for routine diagnosis 3, 4

Critical Diagnostic Pitfall

No clinical or radiographic criteria reliably distinguish HMPV from bacterial infection, necessitating a low threshold for empirical antibiotics in severe cases. 8

• Coinfection with other respiratory viruses (especially RSV) is common and obscures attributable morbidity 8, 9
• Detection of 2-3 pathogens simultaneously is not uncommon in children with lower respiratory tract infections 1, 7

Treatment Approach

Immunocompetent Patients

The standard of care for immunocompetent patients with HMPV infection is supportive management only, as no antiviral agent has established efficacy. 1, 9

• Rest, hydration, and symptomatic management are the mainstays of therapy 9
• Continue regular asthma controller medications without interruption in children with controlled asthma 7
• Use albuterol (short-acting beta-agonist) as needed for wheezing or increased cough, 2 puffs every 4-6 hours 7
• Avoid over-the-counter cough and cold medications in children, as they lack proven efficacy 7
• Oxygen therapy should be titrated to maintain adequate saturation 9
• High-protein, high-vitamin, carbohydrate-containing diets provide nutritional support 9

Immunocompromised Patients

Consider treating HMPV lower respiratory tract disease with ribavirin and/or intravenous immunoglobulin in immunocompromised patients, despite the lack of randomized controlled trial data. 9

• This consideration applies specifically to HSCT recipients and leukemia patients with pneumonia or lower respiratory tract involvement 9
• Upper respiratory tract infection alone in immunocompromised patients does not typically warrant antiviral therapy 9
• For patients developing moderate to severe ARDS, use high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) as initial escalation 9
• Invasive mechanical ventilation with prone positioning is indicated for severe ARDS 9

Severe Disease Management in Children

Administer oral prednisolone 1-2 mg/kg/day for 3-5 days under medical guidance if the child develops tachypnea, chest retractions, or moderate-to-severe respiratory distress. 7

Infection Control Measures

Implement standard and droplet precautions to prevent nosocomial transmission, particularly in healthcare settings. 9

• Asymptomatic shedding rates may be substantial in immunocompromised populations 9
• Prolonged viral shedding has been documented in HSCT patients 9
• Children may return to school when fever-free for 24 hours without fever-reducing medication and feeling well enough to participate in normal activities 7
• Encourage frequent handwashing to prevent spread 7

Warning Signs Requiring Immediate Medical Attention

Seek immediate care for increased breathing rate, visible chest retractions, wheezing unresponsive to albuterol, difficulty speaking in full sentences, decreased activity level, refusal to eat or drink, or unusual tiredness. 7

• Fever persisting beyond 3-4 days or fever returning after initial improvement may indicate complications 7

Current Research and Future Directions

No licensed vaccines or antiviral therapies are currently available for HMPV, though several candidates are in development. 2

• Monoclonal antibodies targeting conserved epitopes of the HMPV fusion (F) protein have shown strong neutralizing activity in vitro and in animal models, though none have reached clinical trials 2
• Vaccine platforms including subunit, live attenuated, vector-based, and mRNA approaches are progressing, with some showing promise in adult populations 2, 4
• Data in children, especially seronegative infants, remain limited 2
• Antiviral research has explored repurposed drugs such as ribavirin and probenecid, along with novel agents like fusion inhibitors, though none are yet approved 2, 4
• Ribavirin has shown activity both in vitro and in animal models but lacks clinical trial validation 4

Key Clinical Pitfalls to Avoid

Do not request or expect antibiotics for confirmed viral HMPV infection, as the virus does not respond to antibiotics and unnecessary use contributes to resistance. 7

• However, maintain a low threshold for empirical antibiotics in severe cases where bacterial coinfection cannot be excluded 8
• Do not stop regular asthma controller medications during viral illness, as this increases exacerbation risk 7
• Do not rely on clinical or radiographic features alone to distinguish HMPV from bacterial pneumonia 8