Human Herpes Virus—Six Related Clinical and Functional Implications in Lung Transplant Patients: Bronco Alveolar Lavage Analysis, Coinfections, Rejection, and Survival

Human herpesvirus 6 (HHV-6) is a common virus that can reactivate in immunocompromised patients, including lung transplant (LT) recipients. This study aimed to evaluate the clinical and functional implications of HHV-6 infection in LT patients through a retrospective analysis of 175 individuals who underwent lung transplantation at the City of Health and Sciences of Turin between 2014 and 2023. Surveillance bronchoscopies-including bronchoalveolar lavage (BAL) and transbronchial biopsies-were performed at scheduled intervals over a two-year period to detect HHV-6 and other pathogens, and to assess acute rejection. Spirometries were performed to evaluate graft function. Among the cohort, 33% of 822 BAL samples tested were positive for HHV-6, with a notable association between high viral load (≥500 copies/mL) and the development of post-transplant lymphoproliferative disorder (PTLD) (13% vs. 1%, <i>p</i> = 0.02) at 1 month and (9% vs. 1%, <i>p</i> = 0.026) at 12 months. Co-infection with CMV (78% in positives vs. 55% in negatives; <i>p</i> = 0.006), Epstein-Barr virus (EBV) (35% vs. 16%; <i>p</i> = 0.010), and bacterial and fungal infection (specifically, a higher rate of isolation of <i>Achromobacter xylosoxidans</i> (13%), <i>p</i> = 0.010) was frequently observed in conjunction with HHV-6 positivity. Notably, patients with at least one HHV-6 positive BAL exhibited a significant reduction in forced vital capacity (FVC) at multiple follow-up points, FVC 82% in positives vs. 92% in negatives (<i>p</i> = 0.038) at 4 months and 87% vs. 98% <i>p</i> = 0.033 at 8 months and 87% vs. 99% <i>p</i> = 0.038 at 24 months. No direct associations with acute rejection or overall survival were found. By means of this study, we provide a wide overview of HHV-6 in lung transplant recipients, filling in a gap of evidence in the field. We report a remarkable incidence and a significant association with acknowledged clinically relevant viral infections, PTLD, and functional tests decline, with no association with mortality.