Emerging human metapneumovirus (hMPV) strains spark concerns and opportunities in managing respiratory infections in kids.

Short Communication: Emerging lineages A2.2.1 and A2.2.2 of human metapneumovirus (hMPV) in pediatric respiratory infections: Insights from India. Image Credit: FOTOGRIN / Shutterstock

In a recent study published in the journal IJID Regions, researchers investigated the role of human metapneumovirus (hMPV) in pediatric respiratory infections.

The study explored the genetic diversity and prevalence of emerging hMPV lineages, particularly A2.2.1 and A2.2.2, in children under five years old, with the aim of enhancing public health understanding and preparedness for respiratory viral outbreaks.

Background

Acute respiratory infections are a leading cause of childhood illness and mortality worldwide, especially in children below five years of age in low- and middle-income countries. Among the pathogens responsible, hMPV significantly contributes to respiratory illnesses, affecting both the upper and lower respiratory tracts.

Based on the genetic diversity, hMPV is categorized into two main groups, A and B, and further divided into lineages such as A2.2.1 and A2.2.2. Global studies have highlighted the evolving nature of these lineages, but information on their prevalence and genetic variability is limited, especially in specific regions of India.

Furthermore, while the coronavirus disease 2019 (COVID-19) pandemic has altered the spread of many seasonal respiratory viruses, its impact on hMPV epidemiology remains underexplored. A comprehensive understanding of hMPV’s genetic characteristics, prevalence, and clinical significance could help inform prevention and control strategies in vulnerable populations. This study also sought to evaluate hMPV’s co-circulation with other respiratory pathogens and its implications for public health interventions.

About the study

In the present study, the researchers examined the prevalence and genetic diversity of hMPV in children under five years of age in Puducherry, India, between January 2021 and June 2024. Children presenting with symptoms of influenza-like illness and acute respiratory infections were enrolled in the study, while those older than five years were excluded.

The researchers collected nasopharyngeal swabs and extracted ribonucleic acid (RNA) from them using a standardized viral RNA isolation kit. Using reverse transcription polymerase chain reaction (RT-PCR), they screened for respiratory pathogens, including hMPV, influenza, and respiratory syncytial virus.

Additionally, during an outbreak of hMPV between November 2022 and March 2023, hMPV-positive samples with low cycle threshold values were analyzed further. The study sequenced the hMPV fusion protein gene to determine genetic lineages, using primers specific to the targeted regions.

The researchers also employed advanced bioinformatics tools to predict glycosylation sites and assess mutations in the fusion protein gene that could influence antigenicity and immune response.
The genetic data were analyzed using phylogenetic methods to categorize samples into recognized hMPV genotypes and subclusters. Mutations associated with novel lineages were mapped against global reference sequences to determine their evolutionary significance.

To assess the virus’s evolutionary pressures, site-specific selection analyses were conducted using statistical methods. The co-circulation of hMPV lineages with other respiratory pathogens was also examined to understand possible interactions. These methods provided comprehensive insights into the molecular epidemiology and genetic evolution of hMPV in the region and presented a basis for assessing the clinical and public health implications.

Major findings

The study found that hMPV significantly contributed to pediatric respiratory infections, with an overall positivity rate of 2.5% among 4519 samples. During the outbreak period between November 2022 and March 2023, hMPV accounted for 43.1% of the respiratory infection cases among children, making it the predominant pathogen.

The majority of infections occurred in children under one year, highlighting the vulnerability of infants to this virus. Common clinical features included flu-like symptoms, wheezing, and respiratory distress, with severe cases presenting as pneumonia or bronchiolitis. The study also noted the prevalence of bilateral crepitations and a male-to-female ratio of 1.8:1 among those affected.

Phylogenetic analysis of 37 hMPV-positive samples revealed that 91.89% belonged to genotype A, primarily the sub-lineage A2.1, while 8.11% were from genotype B. The study also identified novel lineages A2.2.1 and A2.2.2 within genotype A for the first time in India. These lineages exhibited unique mutations, including amino acid substitutions and glycosylation changes, which could be influencing immune evasion and pathogenicity.

In particular, substitutions such as G42V, E96K, and M250R in lineage A2.2.2 were highlighted as significant. The presence of glycosylation sites, such as O-linked glycosylation at position 191, was found to potentially impact antigenicity.

The researchers also documented site-specific selection pressures and observed ongoing genetic evolution in local strains. They also noted that infection rates peaked during December and January, aligning with known seasonality patterns for respiratory viruses.

These findings underscored the genetic diversity of hMPV and its co-circulation with other respiratory viruses, although co-infections were rare. Comparatively, the study’s observed hMPV prevalence aligns with global findings but differs in the documented seasonality and co-infection patterns, highlighting regional variability. The emergence of novel lineages highlighted their potential impact on disease severity, vaccine design, and the need for continuous surveillance to monitor genetic changes.

Conclusions

To summarize, the study confirmed that hMPV was a significant cause of respiratory infections in young children in India and identified the presence of novel lineages A2.2.1 and A2.2.2 in the samples. These findings emphasized the genetic diversity and seasonal prevalence of hMPV and its public health relevance.

The emergence of these lineages, similar to isolates reported in Japan and the United States, underscores the need for international collaboration in surveillance efforts. The researchers stated that continued genetic surveillance and clinical monitoring are essential to understand its evolving patterns and to guide the development of targeted interventions and preventive strategies.