Dynamics of Torque Teno Virus DNA Load in Bronchoalveolar Lavage in COVID-19 associated Acute Respiratory Distress Syndrome

Background: Torque teno virus (TTV) DNA load has been proposed as a surrogate marker of the net state of immunosuppression. While plasma TTV levels have been associated with infection risk and adverse outcomes, the clinical relevance of TTV in the lower respiratory tract of patients with acute respiratory distress syndrome (ARDS) remains unclear. We investigated bronchoalveolar lavage (BAL) TTV dynamics in COVID-19–associated ARDS, including patients treated with extracorporeal membrane oxygenation (ECMO). Methods: This retrospective single-center cohort study analyzed 179 biobanked BAL samples from 50 adults with PCR-confirmed COVID-19 ARDS. TTV DNA was quantified by qPCR. BAL TTV concentrations were compared between ECMO and non-ECMO patients, before and after ECMO explantation, and between ICU survivors and non-survivors. Associations between early BAL TTV levels and outcome were assessed. Results: BAL TTV concentrations increased significantly over time following ICU admission (R 2 = 0.1816; p < 0.0001) but did not differ significantly between ECMO and non-ECMO patients. In paired analyses, a non-significant trend toward higher BAL TTV levels after ECMO explantation was observed (p=0.078). Early BAL TTV concentrations were not associated with ICU mortality or higher rates of pulmonary, bloodstream, fungal infections, or herpesvirus reactivations. Conclusions: In COVID-19–associated ARDS, BAL TTV showed interesting dynamics with regards to time and the use of ECMO but did not predict mortality or secondary infections. These findings support the need for prospective studies integrating plasma and respiratory TTV kinetics with immune profiling but indicate limited clinical utility of BAL TTV as a standalone biomarker.