MICROBIOLOGY

• Human metapneumovirus (hMPV): negative-sense, single-stranded RNA virus, member of Paramyxoviridae described in 2001--closely related to respiratory syncytial virus (RSV).
  • Taxonomy: order Mononegavirales, family Paramyxoviridae, genus Metapneumovirus (first human member), subfamily Pneumovirinae.
• Genetically similar to avian pneumoviruses types C, B and A.
• Human pathophysiology: replication within the respiratory epithelium within the hyaline membrane.

CLINICAL

• A cause of upper and lower respiratory tract infections worldwide, spread by respiratory droplets or fomite vectors.
  
  • Typically causes less severe infection than RSV.
  • Studies suggest seasonality, occurring 1-2 months post-RSV peak (i.e., late winter/ spring).
  • An occasional cause of severe infection (pneumonia, ARDS), especially in immunocompromised individuals.
  • Fourth most common pathogen detected in patients admitted with CAP in many U.S. series.
  • Typical symptoms include cough, fever, rhinorrhea, and dyspnea.
    • May cause bronchiolitis +/- pneumonia
  • Children typically shed the virus for 1 to 2 weeks after the onset of clinical illness.
• Epidemiology: Most children are infected by age 5, and it is a typical cause of respiratory illness in older children compared to RSV.
  
  • First infections typically begin after 6 months of age. Repeated infections are common in childhood.
    • The second most commonly identified virus in RTI (the first is RSV).
    • Re-infection is usually limited to URTI.
    • 30-85% of children hospitalized for hMPV have underlying comorbidities (cardiopulmonary disease, HIV, immunocompromised).
    • Children who develop pneumonia:
      • Parahilar infiltrates are most common (69%), followed by atelectasis (40%), and consolidation is less common (18%)[5].
  • Older individuals (>65 years) may experience severe infection despite high seroprevalence rates.
    • A significant cause of respiratory illness in patients with COPD, asthma, and malignancy.
    • Also found more commonly in immunocompromised patients.
      
      • Pneumonia in up to 40% of hMPV-infected, hospitalized patients.
  • Healthy adults may develop severe PNA.
  • Immunocompromised: Fatal infections are described in cancer and HSCT patients.
• Ddx: other viruses for consideration include RSV (most common), parainfluenza, influenza, adenovirus, bocavirus, rhinovirus, coronavirus.
• Diagnosis:
  • Preferred: Direct detection of viral genome by nucleic acid amplification test (NAAT).
    • Usually part of a multiplex respiratory panel.
  • hMPV antigen detection by immunofluorescent antibody test on sputum is available but less sensitive than PCR.
  • Culture: requires cell culture, difficult and rarely performed.

SITES OF INFECTION

• Respiratory tract:
  
  • Upper: bronchitis, rhinitis
  • Lower: bronchiolitis, croup, pneumonia,
  • ARDS (usually adults)
  • Cause of asthma exacerbation
• GI: occasional reports of diarrhea, vomiting
• Ocular: conjunctivitis
• CNS: Encephalitis is described.

TREATMENT

FOLLOW UP

• Risk factors for infection requiring hospitalization:
  • Age < 6 months
  • Household crowding
• Severe hMPV disease was associated in one study with female sex, prematurity, and genotype B infection[13].
• Rarely is hMPV a fatal illness.

OTHER INFORMATION

• The second most common cause of pediatric viral respiratory tract infection (after RSV).
• Descriptive studies have implicated the virus in many populations, including infants, children, the elderly and patients who have significant comorbidities or are immunocompromised.
• Diagnosis is mostly secured by RT-PCR.
• No routine antiviral treatments have been identified.

References

1. Jobe NB, Rose E, Winn AK, et al. Human Metapneumovirus Seasonality and Co-Circulation with Respiratory Syncytial Virus - United States, 2014-2024. MMWR Morb Mortal Wkly Rep. 2025;74(11):182-187.  [PMID:40179043]

   Comment: hMPV joins RSV and influenza as a respiratory virus that has had an increase, which appears to be related to the COVID pandemic effects on the population.
   

2. Akhmedov M, Wais V, Sala E, et al. Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes. Transpl Infect Dis. 2020;22(4):e13276.  [PMID:32162389]

   Comment: Small single-center retrospective study of outcomes among HSCT recipients with RSV or hMPV (47 patients with RSV and 24 with hMPV) in Germany. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. 11.5% suffered a virus-associated death. Sixty-day mortality was significantly higher in the immunodeficiency scoring index (ISI) high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Treatment of LRTI with intravenous ribavirin resulted in a similar outcome in RSV- and hMPV-infected patients. No benefit detected regarding adjunctive treatment with immunoglobulins.
   Rating: Important
   

3. Vidaur L, Totorika I, Montes M, et al. Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis. Ann Intensive Care. 2019;9(1):86.  [PMID:31342206]

   Comment: A prospective observational study of adult patients admitted with severe hMPV-CAP (n=50) and severe Influenza-CAP (n=109) to a single center in South Korea between 2010 and 2017.
   Mortality was similar between both groups. Oral ribavirin was not associated with improved outcome (60-day mortality: ribavirin therapy group 35.0% [7/20] vs. no ribavirin therapy group 30.0% [9/30], p = 0.71). Subgroup analyses showed no significant differences in mortality among non-immunocompromised and immunocompromised patients.
   Rating: Important
   

4. Choi SH, Hong SB, Huh JW, et al. Outcomes of severe human metapneumovirus-associated community-acquired pneumonia in adults. J Clin Virol. 2019;117:1-4.  [PMID:31128379]

   Comment: Retrospective large cohort study from a single enter in South Korea. The authors compared outcomes of patients admitted with CAP and found to have hMP or flu. hMPV was less common than flu (3.2% vs. 7.0% among 1559 patients with severe CAP). The mortality rates were not significantly different between the two groups (30-day mortality: 24.0% vs. 32.1%, p = 0.30; 60-day mortality: 32.0% vs. 38.5%, p = 0.43). Oral ribavirin therapy was not associated with improved outcome (60-day mortality: ribavirin therapy group 35.0% [7/20] vs. no ribavirin therapy group 30.0% [9/30], p = 0.71). Subgroup analyses showed no significant differences in mortality among non-immunocompromised (60-day mortality: hMPV 25.6% vs. flu 31.1%, p = 0.55) and immunocompromised patients (60-day mortality: hMPV 54.5% vs. 54.3%, p = 0.99). The length of ICU and hospital stay did not differ between groups.
   Rating: Important
   

5. Hilmes MA, Daniel Dunnavant F, Singh SP, et al. Chest radiographic features of human metapneumovirus infection in pediatric patients. Pediatr Radiol. 2017;47(13):1745-1750.  [PMID:28831577]

   Comment: Among children < 5 years, most had parahilar inflitrates if they had an abnormal CXR. Consolidative picture was less common.
   

6. Lim FJ, de Klerk N, Blyth CC, et al. Systematic review and meta-analysis of respiratory viral coinfections in children. Respirology. 2016;21(4):648-55.  [PMID:26919484]

   Comment: The findings of 2 or more viruses in this study, comprising 19 papers, did not indicate an increased severity of illness.
   

7. Hasvold J, Sjoding M, Pohl K, et al. The role of human metapneumovirus in the critically ill adult patient. J Crit Care. 2016;31(1):233-7.  [PMID:26572580]

   Comment: In this study of 128 pts with hMPV infection, 31% required ICU care and hMPV was considered likely cause in 38% and possibly the cause in 55%. ARDs criteria were seen in 48% of these patients. Many of these adult patients had an underlying cardiopulmonary disease but also afflicted some without any co-morbidities.
   

8. Dawood FS, Jara J, Estripeaut D, et al. What Is the Added Benefit of Oropharyngeal Swabs Compared to Nasal Swabs Alone for Respiratory Virus Detection in Hospitalized Children Aged <10 Years? J Infect Dis. 2015;212(10):1600-3.  [PMID:25943205]

   Comment: Nasal swabs recovered hMPV equally as well as oropharyngeal swabs for molecular detection, but using both appears to increase yield by no more than 10%.
   

9. Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-27.  [PMID:26172429]

   Comment: Population-based surveillance study of adults 18 years of age or older requiring hospitalization for community-acquired pneumonia among five hospitals in Chicago and Nashville. The study reveals that viruses were detected in 23% of cases, and co-detection of bacteria and viruses occurred in 3%. hMPV was the third most common virus isolated after rhinovirus and influenza.
   Rating: Important
   

10. Schuster JE, Williams JV. Human Metapneumovirus. Microbiol Spectr. 2014;2(5).  [PMID:26104361]

    Comment: A review article is comprehensive. Some interesting tidbits: 4% of adult infections are asymptomatic. Humoral immunity produced and antibody responses may be cross-protective.
    

11. Haas LE, Thijsen SF, van Elden L, et al. Human metapneumovirus in adults. Viruses. 2013;5(1):87-110.  [PMID:23299785]

    Comment: In adults with pneumonia, typically in elderly or immunocompromised patients, interstitial radiographic changes are observed, along with leukopenia and elevated liver function tests (LFTs). Rates of ICU care, mechanical ventilation, and other similar measures are comparable to those in this population for RSV and influenza.
    

12. Edwards KM, Zhu Y, Griffin MR, et al. Burden of human metapneumovirus infection in young children. N Engl J Med. 2013;368(7):633-43.  [PMID:23406028]

    Comment: A multinational prospective study in children < 5 yrs; HMPV detected in 200 of 3490 hospitalized children (6%), 222 of 3257 children in outpatient clinics (7%), 224 of 3001 children in the emergency department (7%), and 10 of 770 asymptomatic controls (1%). Hospitalized children tended to be older and have diagnoses such as pneumonia or asthma requiring supplemental oxygen. Most children had no underlying chronic health problems. The authors conclude that hMPV results in a significant number of both inpatient and outpatient visits.
    Rating: Important
    

13. Papenburg J, Hamelin MÈ, Ouhoummane N, et al. Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children. J Infect Dis. 2012;206(2):178-89.  [PMID:22551815]

    Comment: A Canadian study found 58 of 305 outpatient children (19.0%) and 69 of 734 hospitalized children (9.4%) infected with hMPV, second only to RSV (48.2% and 63.6%, respectively). In the multivariate regression analysis of hMPV cases, age < 6 months and household crowding were associated with hospitalization. Among hospitalized patients, risk factors for severe hMPV disease were female sex, prematurity, and genotype B infection.
    

14. Schildgen V, van den Hoogen B, Fouchier R, et al. Human Metapneumovirus: lessons learned over the first decade. Clin Microbiol Rev. 2011;24(4):734-54.  [PMID:21976607]

    Comment: Comprehensive review with 263 references highlighting important scientific and clinical advances since the discovery of human metapneumovirus in 2001. There is little evidence to support any specific treatment recommendations. Generally, supportive care is advised. Authors include the discoverer of the virus as well as many key investigators and clinicians.
    

15. Shahda S, Carlos WG, Kiel PJ, et al. The human metapneumovirus: a case series and review of the literature. Transpl Infect Dis. 2011;13(3):324-8.  [PMID:21631655]

    Comment: The authors describe nine patients at their institution who were immunocompromised and suffering from human metapneumovirus infection. They state that two of these patients were successfully treated with ribavirin (aerosolized) and polyclonal human immunoglobulin. I believe they are quite overstating the case that all should be considered for therapy with severe disease given lack of prospective, randomized trials especially given the expense and the difficulties of administering aerosolized ribavirin.
    

16. Williams JV, Edwards KM, Weinberg GA, et al. Population-based incidence of human metapneumovirus infection among hospitalized children. J Infect Dis. 2010;201(12):1890-8.  [PMID:20446850]

    Comment: A study from Nashville, TN in 1104 children hospitalized found HMPV in 3.8% of children with respiratory tract infection or fever. This was similar to the influenza virus and parainfluenza virus 3.
    

17. Johnstone J, Majumdar SR, Fox JD, et al. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.  [PMID:18689592]

    Comment: One of several studies showing that viral coinfection is not infrequent in adults hospitalized for pneumonia. In this multicenter study of 193 patients, 7 (3.6%) had recovery of hMPV.
    

18. Madhi SA, Ludewick H, Kuwanda L, et al. Pneumococcal coinfection with human metapneumovirus. J Infect Dis. 2006;193(9):1236-43.  [PMID:16586360]

    Comment: A hypothesis-generating study suggests that severe hHMPV infection may be due to co-infection with the pneumococcus. Study examined 2715 episodes of LRTI in children, and found in those who were fully immunized with PCV, hMPV-associated LRTI was reduced by 45% (95% confidence interval [CI], 19%-62%; P = .002), and the incidence of clinical pneumonia was reduced by 55% (95% CI, 22%-74%; P = .003). Similarly, in fully vaccinated HIV-infected children, the incidence of hMPV-associated LRTI was reduced by 53% (95% CI, 3%-77%; P = .035), and that of clinical pneumonia was reduced by 65% (95% CI, 19%-85%; P = .020).
    

19. Hamelin ME, Prince GA, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection. Antimicrob Agents Chemother. 2006;50(2):774-7.  [PMID:16436743]

    Comment: The animal model is suggestive that ribavirin with corticosteroids yields some benefit. There is no similar human evidence, so there cannot be any reasonable recommendation for the use of ribavirin at this time.
    

20. König B, König W, Arnold R, et al. Prospective study of human metapneumovirus infection in children less than 3 years of age. J Clin Microbiol. 2004;42(10):4632-5.  [PMID:15472321]

    Comment: Although most viral illnesses in this age group are due to RSV, this study suggests that co-infection with hMPV + RSV yields more severe illness, including those in the ICU.
    

21. van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7(6):719-24.  [PMID:11385510]

    Comment: The initial description of hMPV, isolating the virus from children with unexplained RTIs. Sequencing suggests that the virus is closely related to avian metapneumovirus (a cause of rhinotracheitis and swollen head syndrome in chickens).
    Rating: Important