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Published on: December 10, 2013
Biomarkers for Disease Severity in Children Infected With Respiratory Syncytial Virus: A Systematic Literature Review
Deniz Öner1, Simon B Drysdale2,3,4, Calum McPherson2
1Infectious Diseases Translational Biomarkers, Janssen Pharmaceutica, Beerse, Belgium.
Insights
Biomarkers for severe respiratory syncytial virus (RSV) infection are not yet validated. Further research into epigenetics, metabolomics, and the microbiome is needed for novel RSV biomarkers.
Area of Science:
- Virology
- Immunology
- Biomarker Discovery
Background:
- Clinical manifestations of respiratory syncytial virus (RSV) infection range from mild to life-threatening.
- Current knowledge has gaps regarding biomarkers for objectively defining severe RSV disease and predicting clinical outcomes.
Purpose of the Study:
- To systematically review and synthesize existing literature on biomarkers associated with respiratory syncytial virus (RSV) disease severity.
- To identify gaps in knowledge and highlight areas for future research in RSV biomarker discovery.
Main Methods:
- A systematic literature search was conducted across multiple databases (Ovid Medline, Embase, Global health, Scopus, Web of Science) from 1945 to March 2019.
- 111 studies were included after screening 25,132 abstracts, with risk of bias assessed using the Cochrane tool.
Main Results:
- RSV severity correlated with antibody titers, reduced T and B cells, dysregulated innate immunity, neutrophil mobilization, decreased Th1 response, and a Th2-weighted shift.
- Microbial exposures in the respiratory tract may contribute to neutrophil mobilization in infants with severe RSV.
Conclusions:
- A wide range of biomarkers are associated with RSV disease severity, but robust, validated biomarkers are lacking.
- Heterogeneity in study designs and definitions of severe RSV disease necessitate prospective studies for biomarker validation.
- Future research exploring epigenetics, metabolomics, and microbiome may yield novel RSV biomarkers.
Background:
Clinical manifestations of respiratory syncytial virus (RSV) infection vary widely from mild, self-limiting illness to severe life-threatening disease. There are gaps in knowledge of biomarkers to objectively define severe disease and predict clinical outcomes.
Methods:
A systematic search was performed, 1945-March 2019 in databases Ovid Medline, Embase, Global health, Scopus, and Web of Science. Risk of bias was assessed using the Cochrane tool.
Results:
A total of 25 132 abstracts were screened and studies were assessed for quality, risk of bias, and extracted data; 111 studies met the inclusion criteria. RSV severity was correlated with antibody titers, reduced T and B cells, dysregulated innate immunity, neutrophil mobilization to the lungs and blood, decreased Th1 response, and Th2 weighted shift. Microbial exposures in respiratory tract may contribute to neutrophil mobilization to the lungs of the infants with severe RSV compared with mild RSV disease.
Conclusions:
Although a wide range of biomarkers have been associated with RSV disease severity, robust validated biomarkers are lacking. This review illustrates the broad heterogeneity of study designs and high variability in the definition of severe RSV disease. Prospective studies are required to validate biomarkers. Additional research investigating epigenetics, metabolomics, and microbiome holds promise for novel biomarkers.
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