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. Electronic supplementary material The online version of this article (10.1186/s40635-019-0256-z) contains supplementary material, which is available to authorized users.

Epstein-Barr virus reactivation in sepsis due to community-acquired pneumonia is associated with increased morbidity and an immunosuppressed host transcriptomic endotype

“…Although we observed an increase in 28-day mortality in individuals with EBV reactivation compared to those without (24% vs 16%; p = 0.051), this was on the borderline of statistical significance. This is in keeping with three large studies focusing on sepsis patients 8,9,12 which used PCR to quantify EBV load. These studies did not find an association with EBV reactivation and mortality although one small study of critically ill sepsis and non-sepsis patients 19 did find a positive association.…”

“…Alongside this, studies describing a high frequency of viral reactivation in sepsis patients support the concept that previously immunocompetent individuals can develop a varying degree of functional immunosuppression in response to severe infection [8][9][10][11][12] . Walton and colleagues observed that 43% of septic patients had evidence of viraemia with multiple viruses 8 , the MARS consortium described a 68% frequency of herpesvirus viraemia amongst individuals with septic shock 9 , whilst Mallet and colleagues observed a 53% frequency of herpesvirus viraemia in individuals with septic shock 12 . In both studies, Epstein-Barr virus (EBV) was the most commonly observed reactivated virus at a frequency of 32-48% in plasma 8,9,12 .…”

“…Walton and colleagues observed that 43% of septic patients had evidence of viraemia with multiple viruses 8 , the MARS consortium described a 68% frequency of herpesvirus viraemia amongst individuals with septic shock 9 , whilst Mallet and colleagues observed a 53% frequency of herpesvirus viraemia in individuals with septic shock 12 . In both studies, Epstein-Barr virus (EBV) was the most commonly observed reactivated virus at a frequency of 32-48% in plasma 8,9,12 . Neither group observed an independent association between EBV reactivation and mortality, although the MARS consortium identified a 3.17 hazard ratio for mortality with concurrent cytomegalovirus (CMV) and EBV reactivation 9 , whilst Mallet and colleagues found that reactivation of more than one virus was associated with increased ICU mortality 12 .…”

“…In both studies, Epstein-Barr virus (EBV) was the most commonly observed reactivated virus at a frequency of 32-48% in plasma 8,9,12 . Neither group observed an independent association between EBV reactivation and mortality, although the MARS consortium identified a 3.17 hazard ratio for mortality with concurrent cytomegalovirus (CMV) and EBV reactivation 9 , whilst Mallet and colleagues found that reactivation of more than one virus was associated with increased ICU mortality 12 . In addition, Walton and colleagues observed an increased incidence of fungal infections, mean SOFA score and ICU length of stay in those patients with EBV reactivation 8 .…”

Herpes simplex virus and Cytomegalovirus reactivation among severe ARDS patients under veno-venous ECMO

“…In this retrospective study covering a 5-year period, we found that HSV/ CMV reactivation was frequent and concerned more than half non-immunocompromised patients, which is higher than that described in previous studies including all ICU patients [4,8,14]. This might be explained by several reasons: the use of PCR to diagnose reactivation with a higher sensitivity than older technics, the age of our cohort of patients (with a high probability of seropositivity for HSV and CMV at ICU admission) and the frequency of sepsis with a probable induced "immunoparalysis" [24]. In our cohort, HSV reactivation occurred earlier than CMV reactivation and the median time of reactivation for both viruses was comparable to what is described in "non-ECMO" patients [25].…”