Human metapneumovirus (HMPV): Symptoms, Causes, Complications, Treatment and Prevention

Human metapneumovirus definition

Human metapneumovirus (HMPV) is a common cause of respiratory tract infections in infants, adults, the elderly, and people with impaired immune systems. It can cause cold-like symptoms like runny nose, sore throat and cough, etc. It was first discovered in the Netherlands in 2001 and has since spread worldwide. In 2016, the family was changed from Paramyxovirdae to Pneumoviridae.

This HMPV viral infection is more prominently observed in the winter. It is mainly transmitted through respiratory droplets from people infected with the virus. The virus targets epithelial cells in the respiratory tract, causing inflammation and clinical symptoms. The most common symptoms caused by HMPV infection are upper and/or lower respiratory tract infections, with lower respiratory tract infections being particularly common. Lower respiratory tract infections caused by HMPV can result in pneumonia, bronchiolitis, and acute asthma exacerbations.

As the virus grows slowly in cell culture, molecular techniques (such as reverse transcriptase PCR) are the primary diagnostic tool to detect HMPV. Currently, no vaccine is available, and the treatment is supportive. Pulmonologists or infectious disease specialists often treat HMPV infections, particularly in cases of severe respiratory complications.

Human metapneumovirus meaning

Human metapneumovirus (HMPV) is a negative-sense, single-stranded RNA virus from the Pneumoviridae family. The term "metapneumovirus" is derived from the Greek language, where "meta" means "beyond" or "after," and "pneumon" refers to the lungs, emphasizing its connection to respiratory conditions. HMPV was initially found in 2001 in the Netherlands. It is closely linked to bird metapneumovirus, illustrating its zoonotic origins.

Human metapneumovirus prevalence

Prevalence of HMPV in the World

Human metapneumovirus was first identified in the Netherlands in 2001, causing clinical symptoms in children; however, serological studies showed that this pathogen had already been circulating in the Netherlands since 1958. HMPV infections can occur year-round, but peak prevalence in the northern hemisphere are seen in late winter and early spring. 

These infections occur worldwide and are more prevalent among children, especially those under 2 years old, with an average age of approximately 22 months. 

According to some studies, HMPV accounts for 90 to 100% of children aged 5 to 10. An estimated 142 lakh cases of HMPV-associated acute lower respiratory infections occurred in children worldwide in 2018, emphasising its significant impact on paediatric health.

Prevalence of HMPV in India

In India, the prevalence of Human Metapneumovirus (HMPV) among children with acute respiratory infections varies by area, with rates of 4% in Chennai, 5% in Pondicherry, and up to 12.7% in Vellore. Other studies have observed prevalence rates ranging from 3% to 5% in different locations, demonstrating that HMPV is an unneglectable respiratory infection in paediatric population across the country.

Human metapneumovirus types

Human metapneumovirus (HMPV) is divided into two distinct genetic lineages: Subtype A and Subtype B. Each subtype is then classified into two subgroups, leading to 4 different groups: A1, A2, B1, and B2. These subtypes have varying geographical distributions and can circulate concurrently during outbreaks, adding to the complexity of HMPV epidemiology.

Human metapneumovirus pathophysiology

The pathophysiology of HMPV includes the following: 

• Viral structure: HMPV is a negative-sense single-stranded RNA virus from the Pneumoviridae family. Its genome is similar to that of the respiratory syncytial virus (RSV); however, it lacks certain non-structural genes.

• Infection mechanism: The virus infects airway epithelial cells by binding to them via glycoprotein interactions, particularly with heparan sulfate and other glycosaminoglycans. The fusion (F) protein facilitates the fusion between the viral envelope and the host cell membrane.

• Immune response: Upon infection, HMPV triggers an intense immunological response, including the release of chemokines and cytokines such as IL-6, IFN-alpha, TNF-alpha, and IL-2. This immune reaction can cause inflammation in the respiratory system, which contributes to symptoms like cough, wheezing, and, in extreme cases, bronchiolitis or pneumonia.

• Incubation time: Human metapneumovirus (HMPV) spreads from person to person through respiratory droplets. The incubation time of HMPV lasts 3 to 5 days and varies by individual.
  

Human metapneumovirus causes

Human metapneumovirus (HMPV) is a main respiratory pathogen that mainly affects children but can cause serious illness in vulnerable people. The causes of HMPV infection are distinct, including the following factors:

• Genetic variability: The virus contains different genetic lineages (A and B), with differences that may affect transmission dynamics and infection rates in different populations.



• Zoonotic origins: HMPV is likely to have evolved from avian metapneumoviruses, implying that a zoonotic transmission from birds to humans could be the origin of infection.

• Environmental factors: The virus spreads more frequently during winter and early spring, overlapping with other respiratory infections, which enables its transmission in crowded indoor environments.

• Viral transmission: HMPV is mainly transmitted through respiratory droplets from infected people, especially in close contact situations.
  

Human metapneumovirus symptoms

In general, clinical criteria alone cannot distinguish HMPV infection from other respiratory viruses. Human metapneumovirus can cause either upper or lower respiratory tract infection.

Adult patients with an HMPV infection may be asymptomatic or present with symptoms ranging from mild upper respiratory tract infections to severe pneumonia.

Symptoms of upper respiratory tract infections

• Cough
• Rhinorrhoea (Runny nose)
• Nasal congestion (Stuffy nose)
• Sore throat

Symptoms of lower respiratory tract infections

• Fever
• Wheezing
• Dyspnoea (shortness of breath)
• Hypoxia (low oxygen levels in body tissues)
• Hoarseness
• Purulent cough

Severe symptoms of HMPV

• Pneumonia
• Bronchiolitis
• Asthma
• COPD (chronic obstructive pulmonary disease) exacerbation

Gastrointestinal symptoms of HMPV

• Nausea
• Vomiting
• Diarrhoea
• Otitis media
  

Human metapneumovirus risk factors 

Several risk factors can increase the occurrence of severe HMPV disease. They include the following: 

Modifiable risk factors for human metapneumovirus (HMPV)

These factors can be changed or regulated to decrease the possibility of HMPV infection or severity. The main modifiable risk factors include:

• Exposure to tobacco smoke: Environmental tobacco smoke has been responsible for an increase in respiratory diseases, including HMPV, which emphasizes the need of smoke-free surroundings.

• Household crowding: Increased exposure in crowded living environments may contribute to the spread of HMPV, particularly among children and individuals at risk.

Non-modifiable risk factors for human metapneumovirus (HMPV)

Non-modifiable risk factors are innate characteristics that cannot be altered but influence a person's risk of HMPV. They include:

• Age: Infants under the age of six months, as well as older individuals with weakened immune systems, are significantly more likely to develop severe HMPV illness.

• Premature birth: Because of their immature lungs and immune systems, prematurely born children are more susceptible to severe HMPV symptoms.

• Comorbidities: Individuals with pre-existing medical conditions, such as chronic respiratory diseases or immunosuppression, heart or neural disorders, are more likely to develop serious illness from HMPV.

• Immunocompromised individuals: Patients with weaker immune systems, such as those people undergoing chemotherapy or organ transplantation, have an increased risk of severe symptoms.
  

Human metapneumovirus complications

In certain patient populations, HMPV may result in serious illnesses necessitating hospitalization. The following are the complications associated with HMPV: 

• Bronchiolitis: HMPV is the most common cause of bronchiolitis in children, accounting for nearly 65.7% of hospitalized pediatric patients. It is most common in newborns and young children, frequently necessitating hospitalization for respiratory assistance. 

• Pneumonia: The virus can also lead to pneumonia, which occurs in approximately 14.3% of cases among children infected primarily with HMPV. This condition frequently requires medical attention and can cause considerable morbidity. 

• Respiratory distress and ICU Admission: Severe respiratory distress is typical among hospitalized children with HMPV, with a significant proportion necessitating admission to pediatric intensive care units. Some individuals may require mechanical ventilators or other advanced respiratory assistance.

• Acute respiratory distress syndrome (ARDS) and multiorgan failure: In critical cases, HMPV infection can cause ARDS and multiorgan failure, particularly in children with previous medical conditions or immunocompromised adults. 



• Acute asthma exacerbations: HMPV infection has been linked to asthma exacerbations, which occur in patients after infection. This can lead to higher morbidity in people with pre existing asthma problems.
  

Human metapneumovirus diagnosis

HMPV identification does not require confirmatory tests and is typically based on a clinical diagnosis. However, there are laboratory tests that can be used. Below are the steps involved in diagnosing HMPV: 

• Clinical evaluation 
• Medical history
• Physical examination
• Laboratory testing
• Swab tests
• Nucleic acid amplification tests (NAAT)- Reverse transcriptase-polymerase chain reaction (RT-PCR) 
• Antigen detection tests- Immunofluorescence  assays  and enzyme-linked immunosorbent assays (ELISAs) and direct immunofluorescent-antibody (IFA) test
• Blood tests: Complete blood counts (CBC) and inflammatory markers 
• Serological tests
• Imaging tests
• Chest X-ray or CT scans
• Advanced procedures
• Bronchoscopy
  

Human metapneumovirus treatment

Human Metapneumovirus (HMPV) treatment is mostly supportive, as there are presently no FDA-approved antiviral drugs particularly for this virus. The management options used may differ on the basis of the severity of the infection and the patient's overall condition. The following are the main steps involved in treating HMPV:

• Supportive measures
• Intravenous fluid hydration
• Supplemental oxygen support for hypoxemia via high flow nasal cannula or even mechanical ventilation
• Symptomatic management
• Anti-pyretic medications 
• Bronchodilators 
• Corticosteroids
• Antibiotics for secondary infections
• Antiviral medications
• Ribavirin: Although it is not approved specifically for HMPV infection, ribavirin has shown efficacy in some cases, mainly in immunocompromised patients
• Intravenous Immunoglobulin (IVIG)
• Experimental therapies
• Monoclonal antibodies
• Fusion Inhibitors and RNA Interference
  

Human metapneumovirus prevention

The vaccine for HMPV is currently unavailable. People are advised to practice appropriate personal and environmental hygiene to limit the risk of illness. Below are some of the preventive measures for HMPV: 



Maintaining good hygiene

• Wearing a mask properly, including hand cleanliness before and after use, is essential. 
• Hand hygiene should be practiced regularly, especially before touching one's eyes, mouth, nose; before eating; after using the restroom; after touching public facilities such as handrails or doorknobs; or when hands are contaminated with respiratory secretions from coughing or sneezing.
• When people sneeze or cough, they need to cover their nose and mouth with a tissue paper. They need to throw soiled tissues in a lidded trash bin, then thoroughly wash their hands.
• When experiencing respiratory symptoms, people need to use a surgical mask, stop working or attending school, avoid crowded places, and seek medical attention immediately.
• People must build up their bodies' immunity by eating a balanced diet, exercising regularly, getting enough rest, quitting smoking, and avoiding alcohol.
• Infected individuals are advised to avoid contact with children, older adults, and others with weakened immune systems.
• Individuals are advised to rub both hands with water and liquid soap for at least 20 seconds. Next, rinse with water and dry with a disposable paper towel or hand dryer. If hand washing facilities are unavailable or the hands are not visibly filthy, hand hygiene with 70 to 80% alcohol-based hand rub is an effective solution.

Maintain good environmental hygiene

• Cleaning and disinfecting, eating and drinking utensils after use can help to minimize the transmission of disease.
• Maintaining proper interior ventilation. Avoid crowded or poorly ventilated public settings; high-risk persons are advised to consider using surgical masks.
• Cleaning and disinfecting frequently touched surfaces like furniture, toys, and commonly shared items regularly with household bleach.
• Cleaning away obvious pollutants like respiratory secretions with absorbent disposable towels.
  

Difference between HMPV and COVID

HMPV VS COVID

Though both HMPV and COVID primarily attack the respiratory system, these two viral infections are completely different in terms of severity and fatality. Both viruses transmit through respiratory droplets and contact with infected surfaces. Below are the parameters that help in differentiating HMPV and COVID: