Nasopharyngeal Microbiome Composition and its Clinical Correlates in Children Hospitalized with Severe Pneumonia in East Africa

BACKGROUND: Pneumonia remains the leading cause of infectious mortality in children under 5, with the highest burden in sub-Saharan Africa. Dysbiosis in nasopharyngeal (NP) microbiota may influence pneumonia susceptibility and progression, but little is known about its composition or clinical relevance in low- and middle-income countries. We characterized the NP microbiota of children hospitalized with severe pneumonia in East Africa and investigated associations with clinical outcomes. METHODS: We performed 16S rRNA partial gene sequencing of NP swabs collected at hospital admission from 876 children enrolled in the COAST trial across 5 sites in Kenya and Uganda. Clinical, demographic, and virological data were prospectively collected. Microbial profiles were analyzed using hierarchical clustering, nonmetric multidimensional scaling, and multivariable regression to assess associations with respiratory viral infections, sepsis, cyanosis, bacteremia, coma, HIV status, malnutrition, sickle cell disease, malaria, and mortality. RESULTS: The NP microbiome was structured in 6 distinct clusters, each dominated by different genera, including Staphylococcus, Streptococcus, Haemophilus, Dolosigranulum, Corynebacterium, and Moraxella. Multivariable models adjusting for study site and age showed a positive association between Corynebacterium and early mortality. Temporal analysis showed elevated Corynebacterium abundance in children who died within 48 hours of admission, then declined over longer 56 survival intervals, approaching levels observed in survivors. However, time-continuous models did not support this persistent association, suggesting a subgroup effect. CONCLUSIONS: We provide one of the largest high-resolution surveys of the pediatric upper airway microbiome in Africa, identifying microbial patterns associated with viral infection, HIV status, early death, and bacteremia.