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Human Cytomegalovirus Serostatus Defines Cytokine-Based Predictive Signatures in Sepsis
Frederik Krause1, Birte Dyck2, Kerstin Kappler3
1Ruhr University Bochum, Knappschaft Kliniken University Hospital Bochum, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, 44892 Bochum, Germany.
Pathogens (Basel, Switzerland)
|February 27, 2026
Summary
Human cytomegalovirus (HCMV) serostatus impacts sepsis outcome prediction. Identifying HCMV seropositive patients improves cytokine biomarker accuracy for sepsis survival.
Area of Science:
- Immunology
- Clinical Medicine
- Infectious Diseases
Background:
- Sepsis exhibits heterogeneous immune responses, hindering biomarker prediction of clinical outcomes.
- Latent human cytomegalovirus (HCMV) infection significantly modulates the immune system, potentially affecting sepsis cytokine signaling.
Purpose of the Study:
- To investigate whether HCMV serostatus influences the predictive performance of serum cytokine panels for 30-day sepsis survival.
- To identify specific cytokine profiles associated with sepsis prognosis in HCMV-seropositive and seronegative individuals.
Main Methods:
- Post hoc analysis of 331 patients from the SepsisDataNet.NRW cohort.
- Quantification of 13 serum cytokines and determination of HCMV IgG serostatus via ELISA.
- Nested cross-validated logistic regression with feature selection to identify predictive cytokine panels.
Main Results:
- A four-cytokine panel predicted 30-day survival in the total cohort (AUC=0.66).
- In HCMV-seropositive patients, a two-cytokine panel (IL-10, IL-23) showed improved prediction (AUC=0.69).
- Predictive models failed in seronegative patients (AUC=0.47), with significant survival curve separation only in HCMV-seropositive individuals (p < 0.001).
Conclusions:
- HCMV serostatus defines an immunological context crucial for effective cytokine-based sepsis outcome prediction.
- Incorporating viral serostatus into biomarker discovery can enhance sepsis endotyping reproducibility and biological interpretability.
