Concomitant assessment of immunosuppression and Herpesvirus reactivation in blood at Day 7 after ICU admission in a mixed population - Summary - MDSpire
To assess whether day-7 immunosuppression and blood herpesvirus reactivation, alone or together, were associated with adverse outcomes in a mixed ICU population.
Approach:
Design and population: Exploratory day-7 landmark analysis of 195 REALISM cohort patients who remained in the ICU and had both viral PCR and mHLA-DR measurements.
Biomarker definitions: Immunosuppression (IS+) was mHLA-DR below 8000 AB/C; viral reactivation (VR+) was detectable plasma DNA for at least one of EBV, CMV, HHV6, or HSV1.
Outcomes: The primary endpoint was ICU-acquired infection and/or death by 90 days. Analyses also considered 90-day mortality and sensitivity analyses.
Key Findings:
At day 7, 33% of patients had at least one blood herpesvirus reactivation; 25% of those patients had multiple reactivations.
Low mHLA-DR was significantly associated with adverse outcomes, including in a multivariable model adjusted for age, Charlson Index, and admission SOFA score.
The analyses found no significant association between viral reactivation and adverse outcomes, and no significant outcome difference between VR+ and VR− patients within the immunosuppressed subgroup.
Results were similar across the admission-etiology groups considered and in analyses using 28-day mortality, an mHLA-DR cutoff below 5000 AB/C, isolated EBV reactivation, or patients with sepsis.
Interpretation:
In this mixed ICU cohort, adverse outcomes appeared more closely associated with decreased mHLA-DR than with day-7 blood herpesvirus reactivation. The authors found no evidence that the combination defined a particularly severe patient endotype.
Limitations:
The analysis was exploratory and may have lacked statistical power, particularly in subgroup analyses limited to sepsis or EBV.
Unlike the comparison study, viral status was assessed at a prespecified day-7 time point rather than across the first week, and the cohort included a mixed ICU population.
Viral reactivation at sites outside blood, especially in the respiratory tract, was not assessed.
Conclusion:
The authors describe the findings as hypothesis-generating and state that blood viral reactivation at a specific time point may provide limited additional value as a biomarker of adverse outcomes. They note that this does not exclude a role for viral reactivation in understanding pathophysiology.
