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

Abstract

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. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )