Monitoring of Torque Teno virus DNAemia in critically ill COVID-19 patients: May it help to predict clinical outcomes?

Abstract

Background : Torque teno virus (TTV) DNA load in plasma directly associates with the net state of immunosuppression and inflammation in different clinical settings, including transplantation and chronic inflammatory diseases. Objectives : We investigated whether plasma TTV DNA load may predict the occurrence of certain infectious events and overall mortality in critically ill COVID-19 patients. Patients and Methods : 50 patients (median age, 65.5 years) were recruited. TTV DNA load was quantitated in serial plasma specimens by real-time PCR. Serum levels of interleukin-6, C-reactive protein, ferritin, lactate dehydrogenase, Gamma-Glutamyl Transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) and absolute lymphocyte counts (ALC) in paired specimens were available. Nosocomial bloodstream infections and ventilator-associated pneumonia and overall mortality were the clinical outcomes. Results : TTV DNA was detected in 38 patients (76%). A weak inverse correlation (Rho=-0.28; P = 0.004) was observed between TTV DNA loads and ALC. No direct correlation was found between TTV DNA load and serum levels of any of the above biomarkers. Patients with detectable TTV DNA had an increased risk of subsequently developing infectious events (HR 9.28; 95% CI, 1.29–69.5; P = 0.03). A trend ( P = 0.05) towards higher TTV DNA area under a curve between days 7 and 17 after ICU admission (AUC 7–17 ) was observed in patients who died, as compared to survivors. Conclusion : Our findings suggested that plasma TTV DNA load monitoring may be helpful for predicting the occurrence of severe nosocomial infections and mortality in critically ill COVID-19 patients.

Torquetenovirus viral load is associated with anti‐spike antibody response in SARS‐CoV‐2 mRNA BNT162b2 vaccinated kidney transplant patients

“…Kinetics of TTV DNA load is a potential marker of immune function 8 and has also been investigated in the prediction of severe nosocomial infections and mortality in critically ill COVID 19-patients. 27 The interaction between TTV and viral antigens has already been described. In healthy individuals, TTV load slightly increases after immunologic stimulation with influenza and hepatitis B vaccination.…”

“…Until now, no reliable marker has been identified to quantify the net state of immunosuppression in transplant patients. Kinetics of TTV DNA load is a potential marker of immune function 8 and has also been investigated in the prediction of severe nosocomial infections and mortality in critically ill COVID 19‐patients 27 …”

“…For DNA amplification and quantification, the Argene R‐Gene TTV quantification kit (BioMerieux) was used on an Applied Biosystems 7500 (Thermofisher, Waltham, MA, USA) according to the manufacturer's instructions. The R gene assay is designed to detect the majority of TTV genotypes 1,6–8,10,12,15,16,19,27,28 . The threshold defining positivity was 100 copies/ml.…”

TTV viral load as a predictor of antibody response to SARS COV-2 vaccination

“…Querido et al reported a kidney transplant recipient who had a TTV load of 5.6 log 10 copies/ml, which increased to 7.9 log 10 copies/ml on day 43 after the diagnosis of SARS-CoV-2 infection, when the patient seroreverted ( 1 ). Froque’ et al reported that COVID-19 patients with detectable TTV DNA had an increased risk of subsequently developing infectious events (HR 9.28) and a trend (P = 0.05) toward higher TTV DNA area under a curve between days 7 and 17 after intensive care unit (ICU) admission in patients who died, as compared to survivors ( 2 ). In line with the fact that the most severe presentations of COVID-19 are due to an exaggerated immune response, Solis et al reported that the rate of severe cases was higher in patients with low TTV DNA load in plasma, considering a threshold of 700 copies/ml.…”

Phylogenetic analysis of torque teno virus in Romania: possible evidence of distinct geographical distribution

“…In the last few years, attention shifted from the pathogenic potential of TTV to its potential use as a biomarker. There is strong evidence supporting the use of TTV DNA-aemia as biomarker for monitoring the kinetics of functional immune competence before and after solid organ transplantation [ 15 – 17 ], monitoring the efficacy of antiviral treatments in HIV-infected patients [ 18 ], or even predicting clinical outcome in SARS-CoV-2-infected patients [ 19 ]. However, discriminating between TTV isolates that may be associated with pathology and innocuous isolates should not be overlooked, and genotyping and tracking their distribution thus remain an important task.…”