Transcriptomic Biomarkers Associated with Microbiological Etiology and Disease Severity in Childhood Pneumonia

Background: Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches.

Methods: Using whole blood ribonucleic acid sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed genes that best identified children according to detected microbial pathogens (viral-only vs. bacterial-only and typical vs. atypical bacterial [+/- viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe).

Results: Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial (+/- viral co-detections), and 26 (12%) had atypical bacterial (+/- viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (+/- viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including four genes also identified in the viral-only vs. bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and four genes from the typical vs atypical bacterial model (PRSS23, IFI27, OLFM4, and ABO).

Conclusions: We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.