Blood mNGS-Detected Epstein-Barr Virus in ICU Patients with Pneumonia: Associations with Disease Severity Markers and Inflammatory Burden.

BACKGROUND: Epstein-Barr virus (EBV) is frequently detected in critically ill patients, but the clinical meaning of EBV reported by blood metagenomic next-generation sequencing (mNGS) in ICU patients with pneumonia remains unclear. METHODS: This retrospective secondary analysis used data from a prospective multicenter cohort of patients with suspected sepsis. Data included demographics, clinical variables, radiological findings, blood culture and mNGS results, cytokine levels, and 30-day mortality. RESULTS: A total of 184 ICU patients with pneumonia were included and classified as EBV-positive (n=34) or EBV-negative (n=150) according to blood mNGS. EBV-positive patients had lower serum albumin and systolic blood pressure, higher qSOFA score distribution, more frequent sepsis at enrollment, higher C-reactive protein and procalcitonin levels, higher PaCO2, and lower serum calcium. Pneumocystis jirovecii was numerically more frequent in EBV-positive patients but was not independently associated with EBV positivity after adjustment. In exploratory cytokine analysis, EBV-positive patients showed higher TRAIL levels and more frequent IL-17 detection. In an exploratory multivariable model, lower serum albumin and sepsis at enrollment remained associated with EBV positivity. 30-day mortality did not differ significantly between groups. CONCLUSION: In ICU patients with pneumonia, blood mNGS-detected EBV was associated with markers of disease severity and inflammatory burden. However, these associations do not establish clinically significant EBV reactivation, and no statistically significant difference in 30-day mortality was observed between groups.