Associations Between Sputum Torque Teno Virus Load and Lung Function and Disease Severity in Patients With Chronic Obstructive Pulmonary Disease

Abstract

Purpose: Viral load of Torque Teno virus (TTV) is elevated in immunosuppressed patients. The weakened immune response is typical in chronic obstructive pulmonary disease (COPD) patients. However, the relationship between TTV and COPD is still unknown.Patients and Methods: We enrolled 91 patients admitted to hospitals with acute exacerbation of COPD (AECOPD) between January 2017 and August 2017 (ClinicalTrials.gov ID, NCT03236480). Sputum samples were gathered during hospitalization and the 120-day follow-up. TTV distribution and genogroups were assessed, and the associations between viral loads and clinical parameters were analyzed.Results: TTV DNA was detected in 95.6% of COPD patients, and the viral load was nearly invariable at the stable and exacerbation states. Most TTV DNA-positive patients carried four distinct genotypes. Sputum load of TTV was positively associated with RV/TLC (r = 0.378, p = 0.030), and negatively correlated with FEV1/pre and FEV1/FVC (r = −0.484, −0.432, p = 0.011, 0.024, respectively). Neutral correlation between the TTV DNA load and COPD assessment test (CAT) scores (r = 0.258, p = 0.018) was observed.Conclusion: Sputum loads of TTV DNA could be a novel indicator for lung function and disease severity assessment in COPD patients.

Viruses, friends, and foes: The case of Torque Teno Virus and the net state of immunosuppression

“…58,59 Frye et al observed an unexpectedly high baseline rate of TTV-negative patients in their LuT cohort (67.6%), which was explained on the grounds of differences in PCR sensitivity. 60 To put these figures in context, the presence of detectable TTV viremia in non-transplant patients with chronic conditions leading to end-stage organ failure is estimated at 41.7% 46 to 80% 47 for those on hemodialysis, 95% for those with chronic obstructive pulmonary disease, 61,62 and as high as 100% for those with idiopathic pulmonary fibrosis. 63,64 Of note, these figures are higher as compared to healthy individuals, 32,65 supporting the hypothesis that TTV replication is enhanced not only by impaired immune competence but also by persistent low-grade inflammatory status.…”

Virome in the Lungs: The Role of Anelloviruses in Childhood Respiratory Diseases

“…However, the presence and the high load of TTV have been associated with some acute respiratory diseases both in children and in adults [ 27 , 88 ]. In adults, Xie et al [ 89 ] showed a high prevalence of distribution of torque teno virus (95.6%) in the lungs of 91 patients with COPD, revealing that the observation rate of TTV in COPD is higher than that of other chronic respiratory diseases. Interestingly, the authors stated that an alteration of the immune system in COPD patients could contribute to the high prevalence of TTV, reflecting the immunocompetence of hosts [ 88 , 89 ].…”

“…More recently, in adult patients with coronavirus disease 2019 (COVID-19), the respiratory microbiome was investigated to detect potential changes in the bacterial communities and commensal viruses, such as AVs and redondoviruses, in association with this pathological condition [ 89 , 90 ]; specifically, the authors collected 507 oropharyngeal, nasopharyngeal, and endotracheal samples from 83 hospitalized COVID-19 patients and 75 samples from 13 critically ill patients hospitalized for other diseases, showing an interesting dysbiosis of the lung microbiome in hospitalized patients with COVID-19 compared to other patients. Noteworthy, the authors found that AVs and redondoviruses resulted in being important factors to distinguish patients that were intubated or not [ 89 , 90 ].…”

“…Further investigations are warranted to better define the spatial distribution and the composition of the virome in healthy subjects, the effects of the virome on the lungs, and the virome–host interactions. In conclusion, TTVs are associated with acute respiratory disease or exacerbated chronic lung disease [ 88 , 89 ], and lower CD3+ and CD4+ T cell numbers and higher B cell and eosinophilic counts [ 27 , 37 ] are associated with increased TTV loads. AVs probably have an immunomodulatory activity, and in a suppressed host immune system, they could promote the exacerbation of chronic pulmonary disease, as reported in COPD patients [ 89 ].…”

“…In conclusion, TTVs are associated with acute respiratory disease or exacerbated chronic lung disease [ 88 , 89 ], and lower CD3+ and CD4+ T cell numbers and higher B cell and eosinophilic counts [ 27 , 37 ] are associated with increased TTV loads. AVs probably have an immunomodulatory activity, and in a suppressed host immune system, they could promote the exacerbation of chronic pulmonary disease, as reported in COPD patients [ 89 ]. These findings could lay the groundwork to personalize immunosuppression and antimicrobial prophylaxis treatments.…”