Accepted for/Published in: JMIR Research Protocols
Date Submitted: Nov 25, 2018
Open Peer Review Period: Dec 3, 2018 - Dec 17, 2018
Date Accepted: Mar 3, 2019
(closed for review but you can still tweet)
Aims, study design and enrollment results from the Assessing Predictors of Infant Respiratory Syncytial Virus Effects and Severity (AsPIRES) study
ABSTRACT
Background:
Background:
The majority of infants hospitalized with primary Respiratory Syncytial Virus (RSV) infection have no obvious risk factors for severe disease.
Objective:
Objective:
The AsPIRES (Assessing and Predicting Infant RSV Effects and Severity) study was designed to identify factors associated with severe disease in full-term healthy infants less than 10 months of age with primary RSV infection.
Methods:
Methods:
RSV infected infants were enrolled from three cohorts during consecutive winters from August 2012- April 2016 in Rochester, N.Y. A birth cohort was prospectively enrolled and followed through their first winter for development of RSV infection. An outpatient supplemental cohort was enrolled in the Emergency Department or pediatric offices, and a hospital cohort was enrolled on admission with RSV infection. RSV was diagnosis by reverse transcriptase-polymerase chain reaction (RT-PCR). Demographic and clinical data were recorded, and samples collected for assays: buccal swab (cytomegalovirus PCR), nasal swab (RSV qPCR, complete viral gene sequence, 16S rRNA amplicon microbiota analysis), nasal wash (chemokine/cytokine assays), nasal brush (nasal respiratory epithelial cell gene expression using RNAseq), 2-3 ml of heparinized blood (flow cytometry, RNAseq analysis of purified CD4+, CD8+, B cells and NK cells, and RSV specific antibody). Cord blood (RSV specific antibody) was also collected for the birth cohort. Univariate and multivariate logistic regression will be used for analysis of data using a continuous global respiratory severity score (GRSS) as the outcome variable. Novel statistical methods will be developed for integration of the large complex data sets.
Results:
Results:
453 infants were enrolled into the three cohort; 226 in the birth cohort, 60 in the supplemental cohort and 78 in the hospital cohort. 126 birth cohort infants remained in the study and were evaluated for 150 respiratory illnesses. Of the 60 RSV positive infants in the supplemental cohort 42 completed the study, while all 78 of the RSV positive hospital cohort infnats completed the study. A global respiratory severity score (GRSS) was calculated for each RSV infected infants and is being used to analyze each of the complex data sets by correlation with disease severity in univariate and multivariate methods.
Conclusions:
Discussion: The AsPIRES study will provide insights into the complex pathogenesis of RSV infection in healthy full-term infants with primary RSV infection. The analysis will allow assessment of multiple factors potentially influencing the severity of RSV infection including the level of RSV specific antibodies, the innate immune response of nasal epithelial cells, the adaptive response by various lymphocyte subsets, the resident airway microbiota, and viral factors. Results of this study will inform disease interventions such a vaccines and antiviral therapies. Clinical Trial: none
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