Microbial cell-free DNA sequencing of bronchoalveolar lavage fluid improves diagnostic yield and may add clinical utility in immunocompromised patients with severe pneumonia.

Background: Despite sophisticated standard of care (SOC) testing (including bronchoalveolar lavage (BAL) fluid culture and multiplex PCR), the etiology of pneumonia in immunocompromised patients is frequently unknown. Microbial cell-free DNA (mcfDNA) sequencing increases diagnostic yield in plasma but remains understudied in BAL fluid. Methods: This was a single center, retrospective, observational cohort study. Residual BAL fluid collected from immunocompromised, mechanically ventilated patients with suspected pneumonia was sent to Karius Findings: 228 BAL fluid samples from 155 patients were analyzed. In pneumonia patients, KT-BAL yielded 18 additional Category One organisms, 138 additional Category Two organisms, and 313 additional Category Three organisms compared to SOC. Organisms missed by SOC and identified by KT-BAL included bacterial pathogens (99 patients), clinically relevant DNA viruses (34 patients), non- Interpretation: KT-BAL increased diagnostic yield for immunocompromised patients with suspected pneumonia with suggestion of prolonged respiratory failure in patients with pathogens missed by SOC.