Introduction: Sepsis subphenotypes based on temperature trajectories have been validated in several U.S. healthcare systems, and these subphenotypes have been associated with different outcomes and immune profiles. This study provides the first international external validation of the temperature trajectory subphenotypes.
Methods: Adult ICU non-surgical patients with suspicion of infection hospitalized at The First Affiliated Hospital, Sun Yat-sen University between 2018 and 2024 were included in the study. The following patients were excluded: (1) death or discharge within 24 hours of ICU admission; (2) a diagnosis of COVID-19; or (3) fewer than 3 temperature measurements within three days after infection. Our previous temperature trajectory algorithm was used to classify patients into subphenotypes. Patients’ clinical characteristic and time series immune biomarkers were compared between subphenotypes.
Results: In total, 2,478 patients were enrolled: hyperthermic slow resolvers (HSR) (N=567, 22.9%), hyperthermic fast resolvers (HFR) (N=367, 16.0%), normothermic (NT) (N=780, 31.5%), hypothermic (HT) (N=734, 29.6%). The HT exhibited the highest mortality rate (25%), consistent with previous findings. This was followed by the NT (20%), HSR (17%) and HFR (17%). With NT as reference, HT had significant higher mortality, while no significant differences in the other subphenotypes. The HT group also demonstrated the worst kidney function, as evidenced by the highest AKI stage and the longest duration of CRRT 1.0 (0.0–22.0) h, whereas the other three groups had similar CRRT durations and highest AKI stage. In the 3 days following infection, immune tests shown the HT has the lowest inflammatory response (rapid CRP decline, stable NLR), as well as suppressed adaptive and innate immunity (persistently low lymphocyte counts and mHLA-DR), despite markedly elevated neutrophil counts at baseline that rapidly decreased thereafter.
Conclusions: Temperature trajectory subphenotypes demonstrated similar clinical characteristics, outcomes, and immune profiles in the population of ICU patients in China compared to our previous research. Hypothermic patients, who had the highest mortality rate, also had the lowest levels of innate and adaptive immunity response.
.jpg "Luhao Wang, Ph.D. photo")
