International Validation of Temperature-Trajectory Sepsis Subphenotypes With Longitudinal Immune and Coagulation Patterns and Its Implications for Immunoglobulin Therapy
Authors' conclusion
The temperature-trajectory subphenotypes were validated in an international cohort. Patients in the HT subphenotype exhibited the highest mortality and showed persistent immune dysfunction and coagulopathy. Furthermore, different subphenotypes demonstrated distinct responses to immunoglobulin therapy.
Study context
- Population
- Adult ICU patients with suspected infection, tertiary-care hospital ICU in China
- Participants
- 2,478 patients
- Exposure
- Temperature-trajectory sepsis subphenotypes; immunoglobulin therapy effect by subphenotype
- Hyperthermic slow resolversn = 567
- Hyperthermic fast resolversn = 397
- Normothermicn = 780
- Hypothermic (HT)n = 734
- Outcome
- Validation of temperature-trajectory subphenotypes; interaction between subphenotype and immunoglobulin therapy on 30-day mortality
- Follow-up
- 30 days
Methodological detailsexternal validation, propensity score matching, single-centre
- External validation
- Propensity score matching
- Single-centre
Main finding
As reported in the abstract
Subphenotype distribution and mortality
| Group | Value | Mortality rate |
|---|---|---|
| Hyperthermic slow resolvers | 23% | |
| Hyperthermic fast resolvers | 16% | |
| Normothermic | 31% | |
| HT | 30% | 25% |
Value
Hyperthermic slow resolvers23%
Hyperthermic fast resolvers16%
Normothermic31%
HT30%
Mortality rate
Hyperthermic slow resolvers— not stated in the abstract
Hyperthermic fast resolvers— not stated in the abstract
Normothermic— not stated in the abstract
HT25%
- HT subphenotype had the highest mortality rate, consistent with previous findings
- 25%
Observational data: associations, not effects.
Further findings
| Outcome | HR | P value |
|---|---|---|
| 30-day mortality with immunoglobulin therapy, HT subphenotype (subgroup) · primary subtyping · propensity score matched | 0.47 | P = 0.03 |
Longitudinal immune and coagulation profiles
- HT: lowest inflammatory response (low, rapidly declining CRP; rapidly declining IL-6)
- HT: suppressed immunity (persistently low lymphocyte counts and monocyte HLA-DR)
- HT: coagulation abnormalities (persistently prolonged PT and aPTT; lowest platelets, fibrinogen, hemoglobin; highest rate and dose of RBC transfusion)
30-day mortality with immunoglobulin therapy, HT subphenotype (subgroup)
- Heterogeneous effects of immunoglobulin across subphenotypes; consistent direction of benefit in HT
Original publication
International Validation of Temperature-Trajectory Sepsis Subphenotypes With Longitudinal Immune and Coagulation Patterns and Its Implications for Immunoglobulin Therapy. Crit Care Med. Published 10 June 2026. doi:10.
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