Respiratory virome convergence precedes Hospital-Acquired Pneumonia in critically ill patients

Abstract Hospital-acquired pneumonia (HAP) is one of the most common nosocomial infections, leading to significant morbidity and mortality in critically ill patients. HAP has been previously associated with a dysbiosis of the intestinal and respiratory microbiota. However, the composition of the respiratory virome and its role in HAP pathogenesis remains unclear. Here, we longitudinally analysed the endotracheal virome in 87 critically ill patients, including 47 with HAP. The endotracheal virome was dominated by lytic Caudoviricetes bacteriophages and displayed higher inter- than intra-patient variability. Beta diversity analyses revealed a specific viral convergence toward lower diversity prior to the onset of HAP. Specifically, we identified viral signatures and significant changes in bacteriophages interactions with the core lung microbiome before HAP onset. These results were validated in an independent prospective cohort of 43 patients. Our results demonstrate that changes in the lung virome and in the virus-bacterial interactome precedes HAP induction. These findings suggest an uncovered pathophysiological mechanism of HAP with virome involvement in lung microbiota dysbiosis.