The nasopharyngeal virome in adults with acute respiratory infection

BackgroundRespiratory infections are a leading cause of morbidity and mortality worldwide, with a significant proportion thought to have a viral aetiology. Traditional diagnostic approaches often rely on targeted assays for "common" respiratory pathogens, leaving a substantial fraction of infections unidentified. Here, we used metagenomic next generation sequencing (mNGS) to characterize the nasopharyngeal virome associated with acute respiratory infection (ARI), with and without a positive PCR test result for a panel of common respiratory viruses. MethodsNasopharyngeal swabs from symptomatic outpatients (n=49), of whom 32 tested positive by a multiplex viral PCR, and asymptomatic controls (n=4) were characterized by mNGS. The virome taxa were stratified into human, non-human eukaryotic host, and bacteriophage sub-groups. We used a phage host classification as a proxy to establish bacterial taxa present in the nasopharynx. We then compared the virome biodiversity and presence of pathogens with known respiratory effects across the participant sub-groups. ResultsThe nasopharyngeal virome exhibited similar diversity across the PCR-positive and - negative subsets. Among the top ARI-associated human viruses were enterovirus (16.3%, human rhinovirus, HRV-A), roseolovirus (14.3%, human betaherpesvirus 7, HBV-7) and lymphocryptovirus (8.16%, Epstein-Barr virus, EBV). The top three ARI-associated phage hosts were Streptococcus spp (32.7%), Pseudomonas aeruginosa (24.5%) and Burkholderia spp. (20.4%). The virome of both asymptomatic and symptomatic subjects was also abundant in the Staphylococcus (60.4%) and Propionibacterium (Cutibacterium) acnes bacteriophages (90.6%). The PCR and mNGS results were relatively concordant for human rhinovirus (HRV), but not for other PCR panel targets, including human parainfluenza (HPIV), adenovirus (HAdV), bocavirus (BoV) and seasonal coronavirus (HCoV). ConclusionsmNGS revealed a high diversity of pathogens that could be cause to respiratory symptomatology, either as a single infection or a co-infection between viral and bacterial species. The clinical significance of the mNGS versus multiplex PCR findings warrants further investigation.