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Abstract
Epstein-Barr virus (EBV) reactivation is common in sepsis patients but the extent and nature of this remains unresolved. We sought to determine the incidence and correlates of EBV-positivity in a large sepsis cohort. We also hypothesised that EBV reactivation would be increased in patients in whom relative immunosuppression was the major feature of their sepsis response. To identify such patients we aimed to use knowledge of sepsis response subphenotypes based on transcriptomic studies of circulating leukocytes, specifically patients with a Sepsis Response Signature endotype (SRS1) that we have previously shown to be associated with increased mortality and features of immunosuppression. We assayed EBV from the plasma of intensive care unit (ICU) patients with sepsis due to community-acquired pneumonia. In total 730 patients were evaluated by targeted metagenomics (n = 573 patients), digital droplet PCR (n = 565), or both (n = 408). We had previously analysed gene expression in peripheral blood leukocytes for a subset of individuals (n = 390). We observed a 37% incidence of EBV-positivity. EBV reactivation was associated with longer ICU stay (12.9 vs 9.2 days; p = 0.004) and increased organ failure (day 1 SOFA score 6.9 vs 5.9; p = 0.00011). EBV reactivation was associated with the relatively immunosuppressed SRS1 endotype (p = 0.014) and differential expression of a small number of biologically relevant genes. These findings are consistent with the hypothesis that viral reactivation in sepsis is a consequence of immune compromise and is associated with increasing severity of illness although further mechanistic studies are required to definitively illustrate cause and effect.
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1 Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK (GRID:grid.270683.8) (ISNI:0000 0004 0641 4511)
2 Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382)
3 Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK (GRID:grid.270683.8) (ISNI:0000 0004 0641 4511); Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948)
4 Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK (GRID:grid.270683.8) (ISNI:0000 0004 0641 4511); University of Oxford, Big Data Institute, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948)
5 Adult Intensive Care Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK (GRID:grid.410556.3) (ISNI:0000 0001 0440 1440)
6 William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133)