The Respiratory Microbiome is Linked to the Severity of RSV Infections and the Persistence of Symptoms in Children

Academic Background

Respiratory Syncytial Virus (RSV) is a leading cause of respiratory infections and hospitalizations in infants. While known risk factors for severe infections include preterm birth, congenital heart disease, and bronchopulmonary dysplasia, even healthy full-term infants can develop severe illness from RSV, requiring pediatric intensive care and potentially leading to long-term health issues such as persistent wheezing. The severity of RSV infection can range from a common cold to severe bronchiolitis with respiratory failure, suggesting that other host or environmental factors may modulate disease severity.

Recent studies have found links between early-life respiratory microbial community composition and subsequent risk of respiratory infections. Although the mechanisms are not fully understood, these findings may be explained by microbiota-mediated immunomodulation or immune imprinting from early microbial events. However, it remains unclear whether the early-life microbiome is specifically linked to the severity of RSV infections.

Study Source

This study was conducted by Maartje Kristensen, Wouter A.A. de Steenhuijsen Piters, Joanne Wildenbeest, and others from institutions including the University Medical Center Utrecht in the Netherlands, the University of Edinburgh in the UK, and the University of Turku in Finland. The study was published on December 17, 2024, in Cell Reports Medicine, titled “The Respiratory Microbiome is Linked to the Severity of RSV Infections and the Persistence of Symptoms in Children.”

Study Process

Study Subjects and Sample Collection

The study utilized data from two pediatric cohorts within the European Respiratory Syncytial Virus Consortium (RESCEU), analyzing 1,537 nasopharyngeal samples from 1,135 infants. The study included a birth cohort and a case-control study. The birth cohort involved 797 infants (996 samples), while the case-control study included 257 infants with RSV infection (489 samples) and 52 healthy infants (52 samples).

Samples were collected at various time points: shortly after birth (baseline), during RSV infection, and during the convalescent phase (6-8 weeks post-infection). All samples underwent 16S rRNA sequencing to characterize the bacterial microbiome.

Data Analysis

The study employed linear mixed-effects models and random forest classification models, adjusting for covariates such as age, gender, sequencing depth, and study site. Principal Coordinate Analysis (PCoA) and differential abundance analysis were used to assess differences in microbial communities between healthy controls, RSV-infected individuals, and convalescent samples.

Key Findings

Relationship Between Microbial Diversity and RSV Severity

The study found significant differences in microbial communities between RSV-infected individuals and healthy controls, with greater deviations from a healthy microbiome associated with increased disease severity. Specifically, higher abundances of Haemophilus, Streptococcus, and Moraxella were linked to severe disease and persistent symptoms, while higher abundances of Dolosigranulum and Corynebacterium were associated with milder disease and health.

Association Between Convalescent Microbiome and Persistent Symptoms

During the convalescent phase, the microbial community partially returned to a “healthy” state but remained associated with residual respiratory symptoms. In particular, higher abundances of Haemophilus were linked to persistent symptoms, while a lack of Dolosigranulum was also associated with symptom persistence.

Early-Life Microbiome and RSV Severity

The study found only a modest association between the respiratory microbiome shortly after birth and the severity of subsequent RSV infections. While the early-life microbiome was not linked to the risk of RSV infection, it showed some association with the severity of the infection.

Conclusion

The study highlights that the respiratory microbiome during RSV infection is strongly associated with disease severity and that the microbiome during the convalescent phase remains linked to residual symptoms. The early-life respiratory microbiome, while not predictive of RSV infection risk, shows a modest association with the severity of subsequent infections. These findings provide new insights into the pathophysiology of RSV infections and may inform future treatment and prevention strategies.

Study Highlights

1. Microbiome and Disease Severity: The study found that the respiratory microbiome during RSV infection significantly differs from that of healthy individuals, with greater deviations associated with increased disease severity.
2. Convalescent Microbiome and Symptom Persistence: During the convalescent phase, the microbiome partially returns to a “healthy” state but remains associated with residual respiratory symptoms.
3. Early-Life Microbiome and RSV Severity: Although the early-life microbiome is not linked to the risk of RSV infection, it shows a modest association with the severity of subsequent infections.

Significance of the Study

This large-scale cohort study reveals the association between the respiratory microbiome and the severity of RSV infections, as well as the persistence of symptoms. The findings provide new perspectives on the pathophysiology of RSV infections and may inform future therapeutic and preventive strategies, particularly in the areas of microbiome intervention and personalized medicine.