Microbial Dynamics and Pulmonary Immune Responses in COVID-19 Secondary Bacterial Pneumonia

Secondary bacterial pneumonia (2BP) is associated with significant morbidity following respiratory viral infection, yet mechanistically remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assessed longitudinal airway microbiome dynamics and studied the pulmonary transcriptome of patients who developed 2BP versus controls who did not. We find that 2BP is significantly associated with both mortality and corticosteroid treatment. The pulmonary microbiome in 2BP was characterized by increased bacterial RNA load, dominance of culture-confirmed pathogens, and lower alpha diversity. Bacterial pathogens were detectable days prior to 2BP clinical diagnosis, and in most cases were also present in nasal swabs. Assessment of the pulmonary transcriptome in 2BP patients demonstrated impaired TNF-a signaling and revealed an inverse correlation between bacterial RNA load and innate and adaptive immune gene expression. Together, our findings provide fresh insights into the microbial dynamics and host immune features of 2BP.