Torque Teno Virus Levels During Viral Respiratory Infections: The Interplay With Immune Dysregulation and...

Torque teno virus (TTV) is a ubiquitous, nonenveloped DNA virus of the Anelloviridae family and a proposed surrogate marker of immune competence. Although nonpathogenic, its replication reflects host immune status and is associated with immune dysregulation during respiratory viral infections (RVIs). This study evaluated the interplay among TTV levels, inflammatory, endothelial, and coagulation biomarkers in acute RVIs. We collected 468 leftover material samples (234 respiratory and 234 blood samples) from hospitalized patients with PCR-confirmed RVIs. Patients were stratified by viral etiology, differential involvement of the respiratory tract, age, and possible co-detected pathogens. Cytokines (IL-6, IL-8, IL-1β, TNF-α), IFNs (α/β/γ), and endothelial markers (ICAM-1, VCAM-1) were quantified using microfluidic immunoassays. Routine coagulation parameters were measured in a subset of patients. TTV DNA load was quantified in both compartments using real-time PCR. Associations with inflammatory and coagulation parameters were assessed using nonparametric tests. TTV DNA was detectable across all age groups and viral etiologies, with higher levels in infants (0-1 years) and elderly patients (81-94 years). Blood and respiratory TTV levels were strongly correlated (r = 0.53, p < 0.0001). In infants, blood TTV correlated positively with IL-6 and CRP; in elderly patients, inverse correlations with TNF-α, IFN-α, and ICAM-1 suggested less regulated antiviral and endothelial responses. No significant differences were found by viral type or possible co-detected pathogens, though cytokine-TTV associations persisted. TTV levels reflect systemic and local immune activation during RVIs and deserve further investigation as possible noninvasive biomarker of immune dysregulation and thromboinflammatory risk. Longitudinal studies are needed to determine its prognostic value.