Circulating microbial cell-free DNA is associated with inflammatory host-responses in severe pneumonia
Haopu Yang, Ghady Haidar, Nameer Al‐Yousif, Haris Zia, Daniel Kotok, Asim Ahmed, Lily Blair, Sudeb C. Dalai, Sivan Bercovici, Carine Ho, Bryan J. McVerry, Alison Morris, Georgios D. Kitsios
Abstract
Host inflammatory responses predict worse outcome in severe pneumonia, yet little is known about what drives dysregulated inflammation. We performed metagenomic sequencing of microbial cell-free DNA (mcfDNA) in 83 mechanically ventilated patients (26 culture-positive, 41 culture-negative pneumonia, 16 uninfected controls). Culture-positive patients had higher levels of mcfDNA than those with culture-negative pneumonia and uninfected controls (p<0.005). Plasma levels of inflammatory biomarkers (fractalkine, procalcitonin, pentraxin-3 and suppression of tumorigenicity-2) were independently associated with mcfDNA levels (adjusted p<0.05) among all patients with pneumonia. Such host-microbe interactions in the systemic circulation of patients with severe pneumonia warrant further large-scale clinical and mechanistic investigations.