Objectives: To evaluate the effects of two different levels of positive end-expiratory pressure (PEEP) during helmet continuous positive airway pressure (HCPAP) support on the intubation rate in infants with bronchiolitis admitted to pediatric intensive care units (PICUs). Design: Multicentric prospective, randomized, open clinical trial. Setting: Four tertiary PICUs in Italy. Participants: Infants admitted to PICUs due to severe bronchiolitis and requiring respiratory support. Interventions: The enrolled patients were randomly assigned one of two PEEP levels for HCPAP support: high (P10 group: 10 cmH 2O) or low (P5 group: 5 cmH 2O). Measurements and Main Results: In total, 64 patients were randomly assigned to the P10 group, and 60 to the P5 group. The intubation rate was 9/60 (15%) and 9/64 (14%) in P5 and P10 groups (OR 0.94, 95% CI 0.36-2.46, p=0.99). Of the patients in the P5 group, 47 (78%) were escalated to a PEEP level of 10 cmH 2O. PEEP level was not associated to intubation rate (OR 0.69, 95% CI 0.19 to 2.40, p=0.57), after adjustment for age, gestational age, high flow nasal cannula application, bronchiolitis severity score and pediatric index of mortality 3. No cases of pneumothorax were observed in this study. Conclusions: In this trial on infants with severe bronchiolitis, a PEEP level of 10 cm H 2O during HCPAP in comparison to an initial level of 5 cm H 2O did not show to prevent intubation. These results are not conclusive due to the premature stopping.

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.