Gut Microbiome and Immune Response in Severe RSV Infection in Vietnamese Infants

N/ANot Yet RecruitingNCT07417657

Phuc Huu Phan250 enrolled

Overview

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in young children, and a substantial proportion of severe cases occur in previously healthy infants. The gut-lung axis suggests that gut microbiome composition may modulate respiratory immune responses. This prospective observational study in Vietnam will compare gut microbiome profiles and systemic immune cytokine responses between infants with severe RSV infection and those with mild RSV infection, aiming to identify microbiome-immune signatures associated with disease severity.

This is a single-center, prospective observational study conducted at Vietnam National Children's Hospital in Hanoi over 48 months. Approximately 250 infants aged 1-24 months with RT-PCR-confirmed RSV lower respiratory tract infection will be enrolled and classified into severe vs mild groups based on need for advanced respiratory support (HFNC/CPAP/invasive ventilation) and/or PICU admission versus no/low-flow oxygen requirement. Stool samples collected within the first 24 hours of admission will undergo 16S rRNA sequencing (V3-V4 region) to characterize gut microbiome diversity and taxa abundance. Blood samples collected within the first 24 hours will be used to quantify key cytokines (e.g., TNF-α, IL-6, IL-8, IL-1β, IFN-γ, IL-10, IL-17A, IL-22) using ELISA; immune cell subsets may be assessed by flow cytometry. Clinical severity will be assessed using standardized pediatric scores (PRISM III, PELOD, pSOFA) and treatment outcomes will be recorded. The study will evaluate associations among microbiome features, immune response markers, and RSV severity to propose candidate integrated biomarkers for early risk stratification.

Study Type

OBSERVATIONAL

Enrollment

250

Conditions

Respiratory Syncytial Virus Infection Bronchiolitis

Eligibility

Sex: ALLMin age: 1 MonthMax age: 24 Months

Medical Language ↔ Plain English

Inclusion Criteria: Age 1 to 24 months RT-PCR positive for RSV from respiratory specimen Symptoms consistent with acute lower respiratory tract infection Parent/legal guardian provides informed consent Exclusion Criteria: Prematurity \<32 weeks gestation or birthweight \<1500 g Chronic conditions (e.g., congenital heart disease, chronic lung disease, chronic liver/kidney disease) Primary or acquired immunodeficiency Severe malnutrition (weight-for-age Z-score \< -3 SD) Antibiotic use within 2 weeks before admission Probiotic use within 4 weeks before admission Co-infection with other pathogens (viral/bacterial) Stool sample not obtained within 24 hours of admission

Outcomes

Primary Outcomes

Association between gut microbiome diversity/composition and RSV severity

Differences in gut microbiome diversity and taxonomic composition assessed by 16S rRNA sequencing (alpha diversity, beta diversity, and differential taxa abundance) between severe and mild RSV groups

Time frame: Within 24 hours of hospital admission

Secondary Outcomes

Systemic cytokine response in severe versus mild RSV infection

Serum concentrations of inflammatory and regulatory cytokines (TNF-α, IL-6, IL-8, IL-1β, IFN-γ, IL-10, IL-17A, IL-22) measured by ELISA All cytokines will be measured using the same assay platform and reported in the same unit of concentration. Unit of measurement is pg/ml

Time frame: Within 24 hours of hospital admission

Clinical severity scores in RSV infection measured by Pediatric Sequential Organ Failure Assessment (pSOFA) Score

Clinical severity scores in RSV infection measured by Organ dysfunction severity assessed using the Pediatric Sequential Organ Failure Assessment (pSOFA) score (range: 0-24), with higher scores indicating more severe organ dysfunction

Time frame: within 24 h of hospitalization

Integrated microbiome-immune signature predicting severe RSV

Multivariable model performance (AUC/ROC; or adjusted odds ratios for selected taxa + cytokines)

Time frame: Baseline (first 24h) predicting severity classification during index hospitalization

ICU resource utilization

ICU-free days: calculated as 28 minus ICU length of stay for patients discharged alive before Day 28; assigned 0 for patients who die before Day 28 or remain in ICU on/after Day 28. Ventilator-free days: calculated as 28 minus days of invasive mechanical ventilation for patients alive and ventilated \<28 days; assigned 0 for patients who die before Day 28 or remain ventilated on/after Day 28. Vasopressor-free days: calculated as 28 minus days receiving vasoactive agents for patients alive and requiring vasoactives \<28 days; assigned 0 for patients who die before Day 28 or remain on vasoactives on/after Day 28. Discontinuation requires ≥12 hours without vasoactive support

Time frame: Up to day 28