Torque Teno Virus in Bronchoalveolar Lavage Fluid of Hematological Patients and Association With Pathogens

Torque teno virus (TTV) replication is tightly modulated by the host immune response. As such, TTV viremia has been investigated as a biomarker of immune competence for monitoring the risks of allograft rejection and opportunistic infections in solid organ transplant recipients. We aimed to investigate the associations between TTV levels in bronchoalveolar lavage fluid samples (BALF) and pathogen detection in patients with hematological diseases with suspicion of lower respiratory tract infection (LRTI). TTV DNA was quantified in BALF using qPCR. Linear and logistic regressions were used to study associations between TTV levels in BALF and patients' characteristics, cytological patterns and pathogen detection. A total of 330 BALF from 272 patients with hematological malignancies were included. TTV DNA was detected in 44.5% of samples. The median TTV viral load (VL) in positive samples was 6.24 log copies/mL (IQR: 4.68-7.66). Strong positive associations were found between TTV levels in BALF and a diagnosis of lymphoma, a neutrophil fraction > 3% of BALF cells, and the detection of at least one respiratory virus. To a lesser extent, allogeneic hematopoietic stem cell transplantation, significant bacterial growth in BALF culture, and cytomegalovirus detection in BALF were also associated with TTV levels. We identified in this study multiple associations with TTV VL in BALF. These findings suggest that high TTV levels in BALF could reflect an impaired local immune status, and correlate with the risk of viral LRTI in immunocompromised patients.