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Updated: Jan 13, 2026
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A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
474
Prognostic Relevance of Inflammatory Subphenotypes in Immunocompromised Patients With Sepsis
Melanie F Weingart1, Andrew Willmore1, Hanjing Zhuo1
1Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA.
Critical Care Medicine
|October 28, 2025
Summary
Preexisting immunocompromise, particularly hematologic malignancy, is linked to the hyperinflammatory sepsis subphenotype. This immune status may affect how well sepsis subphenotypes predict patient survival.
Area of Science:
- Critical Care Medicine
- Immunology
- Genomics
Background:
- Sepsis and acute respiratory distress syndrome exhibit distinct molecular subphenotypes.
- These subphenotypes, hyperinflammatory and hypoinflammatory, show varied mortality and treatment responses.
- The role of preexisting immunocompromise in sepsis subphenotype development and prognosis remains unclear.
Purpose of the Study:
- To investigate the association between immunocompromise and the hyperinflammatory sepsis subphenotype.
- To determine if molecular subphenotypes' prognostic relevance extends to immunocompromised populations.
Main Methods:
- Observational cohort study utilizing prospective data from two US intensive care unit (ICU) cohorts.
- Included 1826 patients from combined sepsis cohorts.
- Defined immunocompromise and used latent class analysis for subphenotype assignment; logistic regression and survival analysis were employed.
Main Results:
- Hematologic malignancy showed a strong association with the hyperinflammatory subphenotype (OR, 4.3; p < 0.0001).
- Solid organ transplant history was also associated (OR, 1.6; p = 0.02), but significance was lost after adjusting for bacteremia.
- The hyperinflammatory subphenotype correlated with decreased survival in hematologic malignancy patients.
Conclusions:
- Preexisting immune status significantly influences sepsis subphenotype assignment.
- Immune status may modify the prognostic utility of identified sepsis molecular subphenotypes.
