No association between Epstein-Barr Virus serostatus and infection-related mortality in 9,429 British adults: a UK Biobank study.

OBJECTIVES: Epstein Barr Virus (EBV) is a necessary but not sufficient antecedent to the development of Multiple Sclerosis (MS). This observation has prompted interest in generating a sterilising EBV vaccine to reduce MS incidence. EBV is highly prevalent worldwide, establishing lifelong latency within B cells, and promoting their survival. This has raised concerns that administering EBV vaccines to the general population might have a detrimental impact on humoral immunity. We therefore hypothesised that EBV serostatus is associated with infection-related mortality. METHODS: The study population was derived from the UK Biobank (UKB), a longitudinal cohort study consisting of ∼ 500,000 participants. We leveraged serological data, available in a subset of UKB participants, to define EBV serostatus. A Cox proportional hazards model was used to investigate whether EBV serostatus influenced infection-related mortality. The primary analysis model adjusted for age, sex and Townsend deprivation index. Using linked death registry data, we defined infection-related mortality based on the International Classification of Diseases, Tenth Revision (ICD10) list for primary and contributory cause of death. In sensitivity analyses we accounted for the impact of smoking and body mass index, considered a matched cohort, considered EBV antibody titres as continuous exposures, and considered a more stringent definition for EBV seronegativity. RESULTS: We discovered no evidence of association between EBV seropositivity and infection-related mortality (HR = 1.6, 95% CI = 0.65-3.91, p = 0.30). The absence of association was not materially altered when additionally adjusting for smoking and BMI, modelling EBV serostatus with quantitative antibody levels, conducting a matched cohort analysis, or using a stricter definition for EBV seronegativity. CONCLUSION: Our findings indicate that EBV serostatus is not associated with infection-related mortality in a large, UK population-based cohort of older adults.