High Torque teno virus viremia predicts long-term mortality and reflects chronic low-grade inflammation...

Torque teno virus (TTV) is a ubiquitous virus whose viremia increases in conditions of immune dysfunction and aging, suggesting its potential role as a biomarker of immunosenescence. This study investigated the association between TTV viremia and all-cause mortality risk over seven years in a hospitalized older cohort, and its relationship with inflammatory markers including osteopontin (OPN) and growth differentiation factor 15 (GDF15). Data from 956 patients were analyzed, with high TTV load defined as ≥5 log DNA copies/mL. High TTV viremia was significantly associated with increased mortality risk at 1, 3, and 7 years independently of age, sex, comorbidities, and inflammatory markers. In stratified analyses, this association was significant at one year in both males and females, but persisted at three and seven years only in males. The strongest association was observed in participants aged 80-89 years, remaining significant across all follow-up periods. When patients were stratified by a composite immune score reflecting degrees of immunosenescence, high TTV viremia predicted increased mortality among those with intermediate or severe immune dysfunction, persisting up to seven years in the most immunosenescent subgroup. Patients with elevated TTV loads exhibited increased erythrocyte sedimentation rate (ESR), decreased serum albumin and hemoglobin, and significantly higher plasma levels of OPN and GDF15, whereas IL-10 tended to decrease. No significant differences were observed for neutrophil-to-lymphocyte ratio, IL-6, CD163, CCL22, or CXCL9 between high and low TTV viremia groups. These findings indicate that high TTV viremia independently predicts mortality risk and reflects a pro-inflammatory and immunosenescent state.