Early herpes and TTV DNAemia in septic shock patients: a pilot study

Abstract

Background: Septic shock patients exhibit an increased incidence of viral reactivation. Precise timing of such reactivation-as an early marker of immune suppression, or as a consequence of the later-is not known precisely. Here, using a fully designed nucleic acid extraction automated procedure together with tailored commercial PCR kits, we focused on the description of early reactivation within the first week of ICU admission of several herpes viruses and Torque Teno virus (TTV) in 98 septic shock patients.

Results: Most of septic shock patients had at least one viremia event during the first week (88%). TTV and herpesviruses were detected in 56% and 53% of septic shock patient, respectively. The two most frequent herpesviruses detected within the first week were EBV (35%) and HSV1 (26%). Different kinetic were observed among herpesviruses, faster for EBV and HSV1 than for CMV and HHV6. Although no association was found between herpes viremia and secondary infections, patients with herpesviridae-related viremia were more severe, e.g., higher SOFA scores and plasma lactate levels. While reactivating only 1 virus was not associated with mortality, patients with multiple viremia events had higher ICU mortality. Surprisingly, EBV + TTV early reactivation seemed associated with a lower D28 mortality. No clear association was observed between viremia and immune biomarkers.

Conclusion: Applying a semi-automated process of viral DNAemia determination to this cohort of 98 patients with septic shock, we observed that the number of patients with positive viremia increased during the first week in the ICU. Of note, there was no improvement in predicting the outcome when using viremia status. Nevertheless, this pilot study, introducing standardized procedures from extraction to detection, provides the basis for future standardized diagnostic criteria. A prospective longitudinal clinical study using these procedures will enable determination of whether such viremia is due to a lack of a latent virus control by the immune system or a true clinical viral infection.

Keywords: Biomarker; CMV; EBV; HHV-6; HSV1; Herpes viruses; Immunosuppression; Mortality; Sepsis; TTV.

Fig. 1

DNAemia during the first week following admission. a Number of patients presenting single- or multiple-positive herpes and/or TTV viral DNAemia during the first 6 days following admission in the ICU. Occurrence of each type of herpes virus (HV) or TTV is depicted in the orange boxes. Co-occurrence of HV with other HV or TTV is reported in white boxes. b Venn diagram illustrating single versus multiple viral reactivations; 12 patients presented with no viral event. c Cumulative incidence of individual or collective HV and TTV DNAemia at days 1, 3, and 6 following admission in the ICU