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

Abstract

there was a 24% incidence of EBV reactivation. Six individuals showed simultaneous reactivation of EBV and a second virus. Plasma sampling was enriched for earlier time points (Day 1 = 302; Day 3 = 284; Day 5 = 171).

Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study

“…Additionally, high early TTV viraemia was associated with immune alteration. Single viraemia was more frequent than viraemia from multiple viruses, as previously observed using metagenomic sequencing (16), and the percentage of ICU patients who had at least one Herpesviridae-related viraemia increased over time, as noted by others (9,13). Our study adds to the literature evaluating herpesviruses reactivation in patients with critically ill conditions including sepsis summarised in Table 5.…”

“…It is worth noting that individuals who went on to develop EBV reactivation appeared to present with more severe immune alteration. Consistent with these results, it was recently shown that EBV reactivation in sepsis was correlated with the SRS1 immunocompromised sepsis transcriptomic endotype ( 16 ). During the first week, TTV DNAemia appeared specifically associated with modulation of the lymphoid compartment, including decreased T cells and high expression of IL15 associated with high TTV titre.…”

“…The association between several herpesviruses and worse outcomes has been widely observed in the literature ( 14 , 16 , 41 , 42 ). We observed a similar association with patients that had at least one herpesvirus viraemia during the month: these patients were more severely unwell, with worse outcomes such as mortality and the occurrence of ICU acquired infection.…”

“…EBV reactivation in sepsis was associated with an increased risk of mortality ( 10 , 13 ) and was also observed in a diverse group of ICU patients ( 14 ). Recently, detection of EBV in patients with sepsis due to community-acquired pneumonia was associated with sepsis response signature (SRS) endotype, previously shown to be associated with increased mortality and features of immunosuppression ( 16 ). Similarly, an increase ICU mortality was associated with the detection of HSV-1 ( 17 , 18 ) and CMV ( 19 ), whilst CMV detection in ICU patients was also associated with nosocomial infections ( 19 ).…”

Viral Micro-RNAs Are Detected in the Early Systemic Response to Injury and Are Associated With Outcomes in Polytrauma Patients

“…In a multivariate model considering PtP's cytokines and chemokines as well as viral miRNAs on the day of injury, EBV and KSHV miRNAs were independently predictive of CR. Growing evidence suggests that both KSHV and EBV have the potential to reactivate from latency during times of stress (9,11,14,15,31,32). The high occurrence of patients with detectable miR-BHRF-1 in this study's PtPs and HCs is expected given that EBV infection is ubiquitous (33).…”