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.

Keywords: COVID-19; Intensive care unit; Mortality; TTV DNAemia; Torque teno virus (TTV).

Fig. 1

Whisker plots depicting plasma TTV DNA loads and absolute lymphocyte counts in critically ill COVID-19 patients. The number of specimens available for analyses at different timepoints following intensive care unit admission is shown.

Fig. 2

Correlation between plasma TTV DNA load and absolute lymphocyte counts in critically ill COVID-19 patients. Rho and P values are shown.

Fig. 3

Correlation between plasma TTV DNA load and levels of interleukin-6, ferritin, Dimer-D and lactate dehydrogenase in paired sera in critically ill COVID-19 patients. Rho and P values are shown.

Fig. 4

Correlation between plasma TTV DNA load and levels of Gamma-Glutamyl Transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) in paired sera in critically ill COVID-19 patients. Rho and P values are shown.

Fig. 5

Whisker plots depicting plasma TTV DNA load area under a curve (AUC) between day 7 to day 17 (medians) after ICU admission (AUC7–17), reported as copies x day x mL-1) in critically ill COVID-19 patients who either died or survived. The P value is shown.