Genomic surveillance for community-acquired pneumonia of unknown etiology in children

Objectives The etiologic pathogen is unknown for many pediatric community-acquired pneumonia (CAP) cases. We aimed to identify the causes of CAP of unknown etiology (CAP-UKN) using broad-panel targeted next-generation sequencing (tNGS). Methods A prospective surveillance study was conducted across 26 hospitals in Korea (September 2023 to November 2024). CAP cases with no identified pathogen were defined as CAP-NPD; cases wherein no pathogen or only human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), or normal colonizing bacteria were detected were classified as CAP-UKN. Residual respiratory specimens were analyzed using 16S rRNA sequencing and tNGS. Results Among 605 pediatric CAP cases, 178 (29.4%) had CAP-UKN, including 77 CAP-NPD. CAP-NPD was more common at ages 5-10 years with clinical features similar to Mycoplasma pneumoniae pneumonia. HRV/HBoV/HCoV-positive cases resembled those of viral pneumonia. 16S rRNA sequencing and tNGS identified additional pathogens in 23.8% and 70.8% of CAP-UKN specimens, respectively: Haemophilus influenzae, Moraxella catarrhalis , and viridans streptococci (6.3% each) by 16S rRNA sequencing, and Streptococcus pneumoniae (45.5%) and betaherpesvirus (5.2%) by tNGS. Conclusions Pediatric CAP-UKN may be associated with undetected or atypical pathogens. HRV, HCoV, or HBoV infections may contribute to some pediatric CAP cases in which no other pathogen is detected.