Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients

C Langelier; MS Zinter; K Kalantar; GA Yanik; S Christenson; B Odonovan; C White; M Wilson; A Sapru; CC Dvorak; S Miller; CY Chiu; JL DeRisi

Ten patients with negative conventional testing were found to have microbes of unlikely or uncertain pathogenicity. Notably, each of these patients had potential alternative explanations for their respiratory symptoms. While one of these patients had bacteremia/sepsis, the remaining nine had acute and/or chronic GVHD, underlining the importance of non-infectious alloreactive inflammation in post-HCT pulmonary complications. mNGS identified several viruses with DNA genomes, however only five of these also had well-defined evidence of active replication marked by detectable RNA transcripts (HSV, human papilloma virus and torque teno viruses (TTV, n=3). TTV was the most commonly detected DNA virus, a finding consistent with prior reports demonstrating an increased prevalence of this presumptively innocuous constituent of the human virome in immunosuppressed patients (44) .