Efficacy of Intravenous Immunoglobulin versus Placebo in Combination with Standard Care for Children with Severe Adenoviral Pneumonia: A Randomised, Double-Blind, Multicenter Trial

Rationale/Gaps in Existing Knowledge: Viral pneumonia is a critical issue in children in the PICU. Adenovirus causes up to 10% of global respiratory infections in children, with high mortality in infants and immunocompromised patients. IVIG may help due to its immunomodulatory effects, but no formal guidelines or trials exist for its use in adenoviral pneumonia.

Novelty: IVIG in severe adenoviral pneumonia could reduce morbidity and mortality with minimal toxicity.

Objectives: Compare morbidity and mortality in children with adenoviral pneumonia receiving IVIG versus those not receiving IVIG.

Methods: Children with suspected viral pneumonia needing respiratory support will receive oxygen, ventilators, drugs, fluids, and antibiotics. Nasopharyngeal swabs or aspirates will be collected from non-ventilated children, and mini-BAL samples from those with invasive ventilation. These will be tested for adenovirus using the BIOFIRE panels. Participants will be randomly assigned to receive either IVIG (2g/kg over 2 days) or a placebo. The primary endpoint is the time to clinical improvement up to day 28, defined by a reduction of two levels on a six-point ordinal scale or discharge alive. Secondary outcomes include mortality, ventilator support, vasopressor therapy, hospitalization duration, organ dysfunction, and other complications. Primary analysis will use an intention-to-treat basis, and safety analysis will include all who started treatment. This trial will be registered with ClinicalTrials.gov.

Expected Outcomes: Differences in the outcome between the two groups will provide useful information for the use and recommendation of intravenous immunoglobulin in severe adenoviral pneumonia in children.