Development of a Global Respiratory Severity Score (GRSS) for Respiratory Syncytial Virus Infection in Infants

Caserta, Mary T.; Qiu, Xing; Tesini, Brenda; Wang, Lu; Murphy, Amy; Corbett, Anthony; Topham, David J.; Falsey, Ann R.; Holden‐Wiltse, Jeanne; Walsh, Edward E.

doi:10.1093/infdis/jiw624

Cited by 38 publications

(81 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Illness severity was graded from 0 to 10 using a Global Respiratory Severity Score (GRSS), as previously described. [21] 6 Nasal RNA processing: The process for nasal RNA recovery was previously described. [20] Briefly, following flushing of the nares with saline to remove mucus and cellular debris, a flocked swab was used to recover cells at the level of the turbinates.…”

Section: Methodsmentioning

confidence: 99%

Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants

Wang

Chu

McCall

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

word count: 243. Text word count: 3037 3 AbstractBackground: RSV infection is common in infants, with a majority of those affected displaying mild clinical symptoms. However, a substantial number of infants infected with RSV develop severe symptoms requiring hospitalization. We currently lack sensitive and specific predictors to identify a majority of those who require hospitalization.Method: We used our previously described methods to define comprehensive airway gene expression profiles from 106 full-tem previously healthy RSV infected subjects during acute infection (day 1-10 of illness; 106 samples), and during the convalescence stage (day 14-28 of illness; 69 samples). All subjects were assigned a cumulative clinical illness severity score (GRSS). High throughput RNA sequencing (RNAseq) defined airway gene expression patterns in RSV infected subjects. Using AIC-based model selection, we built a sparse linear predictor of GRSS based on the expression of 41 genes (NGSS1). Using a similar statistical approach, we built an alternate predictor based upon 13 genes displaying stable expression over time (NGSS2). We evaluated predictive performance of both models using leave-one-out cross-validation analyses.Results: NGSS1 is strongly correlated with the disease severity, demonstrating a naïve correlation (ρ) of ρ=0.935 and cross-validated correlation of 0.813. As a binary classifier (mild versus severe), NGSS1 correctly classifies 89.6% of the subjects following crossvalidation. NGSS2 has slightly less, but comparable, prediction accuracy with a crossvalidated correlation of 0.741 and cross-validated classification accuracy of 84.0%.Conclusion: Airway gene expression patterns, obtained following a minimally-invasive procedure, have potential utility as prognostic biomarkers for severe infant RSV infections.

show abstract

Section: Methodsmentioning

confidence: 99%

Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants

Wang

Chu

McCall

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…All rights reserved. For permissions, please email: journals.permissions@oup.com 1 Journal of Tropical Pediatrics, 2019, 0, 1-10 doi: 10.1093/tropej/fmz055 Best Evidence Topics respiratory distress and/or hypoxia [3,4]. The decision to admit a child with a diagnosis of bronchiolitis is based on a combination of history and clinical examination with particular attention on observed or reported apnoea, persistent oxygen saturation <92%, inadequate oral fluid intake and severe respiratory distress [3].…”

Section: W H a T I S A L R E A D Y K N O W N ?mentioning

confidence: 99%

Can a Respiratory Severity Score Accurately Assess Respiratory Distress in Children with Bronchiolitis in a Resource-Limited Setting?

Hakizimana

Saint

Miert

et al. 2019

Journal of Tropical Pediatrics

View full text Add to dashboard Cite

show abstract

“…RSV infected infants were identified and enrolled into the Assessing Predictors of Infant RSV Effects and Severity (AsPIRES) study during three winter (2013-14, 2014-15, and 2015-16) in Rochester NY as previously described 33,34 . All infants were less than 10 months of age at the time of primary RSV infection and came from one of three cohorts;…”

Section: Study Subjectsmentioning

confidence: 99%

“…The severity of the clinical illness in these patients was defined by a global respiratory severity score (GRSS) 33 . Briefly, a Global Respiratory Severity Score (GRSS) was defined by a weighted combination of 9 clinical measures including general appearance, presence of rales, wheezing, cyanosis, retractions, lethargy, poor air movement, maximal age-adjusted respiratory rate, and worst room air oxygen saturation.…”

Section: Defining Illness Severitymentioning

confidence: 99%

“…Subjects were assigned a continuous Global Respiratory Severity Score (GRSS) as previously described 33 . There was no association between severity (defined as being hospitalized or by GRSS) and RSV strain, family-reported environmental tobacco smoke exposure, or the presence of other viral pathogens or bacterial colonization based on a positive RT-PCR (Table 1).…”

Section: Subject Demographicsmentioning

confidence: 99%

See 1 more Smart Citation

Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

Chu

Qiu

McCall

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. Other than age at the time of infection, the causes and correlates of severe illness in infants lacking known risk factors are poorly defined. We recruited a cohort of confirmed RSV-infected infants and simultaneously assayed the presence of resident airway microbiota and the molecular status of their airways using a novel method. Rigorous statistical analyses identified a molecular airway gene expression signature of severe illness dominated by excessive chemokine expression. Global 16S rRNA sequencing confirmed an association between H. influenzae and clinical severity. Interestingly, adjusting for H. influenzae in our gene expression analysis revealed an association between severity and airway lymphocyte accumulation. Exploring the relationship between airway gene expression and the time of onset of clinical symptoms revealed a robust, acute activation of interferon (IFN) signaling, which was absent in subjects with severe illness. Finally, we explored the relationship between IFN activity, airway gene expression and productive RSV infection using a novel in vitro model of bona fide pediatric human airway epithelial cells. Interestingly, blocking IFN signaling, but not IFN ligand production, in these cells leads to increased viral infection. Our data reveal that acute airway interferon responses are physiologically relevant in the context of infant RSV infection and may be a target for therapeutic intervention. Additionally, the airway gene expression signature we define may be useful as a biomarker for efficacy of intervention responses. All rights reserved. No reuse allowed without permission.

show abstract

Development of a Global Respiratory Severity Score (GRSS) for Respiratory Syncytial Virus Infection in Infants

Abstract: Using routine clinical variables, we developed a severity score for infants with RSV infection that should be useful as an end point for investigation of disease pathogenesis and as an outcome measure for therapeutic interventions.

Cited by 38 publications

References 19 publications

Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants

Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants

Can a Respiratory Severity Score Accurately Assess Respiratory Distress in Children with Bronchiolitis in a Resource-Limited Setting?

Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

Contact Info

Product

Resources

About