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Sepsis-associated lymphopenia: Dynamic evaluation and its association with recurrent sepsis in critically ill
Verónica Monzón1, Iván Huespe2, Ernestina Angarola3
1Hospital Italiano de Buenos Aires - Sede San Justo, San Justo, Buenos Aires, Argentina.
Objectives:
To evaluate whether early lymphocyte trajectories, integrating both the depth and duration of lymphopenia, predict recurrent sepsis in critically ill adults.
Design:
Retrospective two-center cohort study.
Setting:
Intensive care units of two tertiary hospitals.
Patients Or Participants:
Adult patients admitted with sepsis or septic shock between January 2011 and July 2024.
Interventions:
None.
Main Variables Of Interest:
Early lymphopenia during the first 48 h was quantified as: (1) number of days with absolute lymphocyte count (ALC) ≤1000 or ≤500 cells/µL, and (2) 48-h time-weighted average lymphocyte count (TWA-L). Recurrent sepsis, defined as a new septic episode occurring ≥7 days after the index event, was analyzed using Fine-Gray competing-risk models, treating death without recurrence as a competing event.
Results:
Among 4701 patients, 429 (9.1%) developed recurrent sepsis and 972 (20.8%) died without recurrence. Profound lymphopenia (ALC ≤ 500 cells/µL) showed a dose-response relationship: compared with 0 days, 1 and 2 days were associated with adjusted subdistribution hazard ratios (sHRs) of 1.61 (95% CI 1.22-2.13) and 2.22 (95% CI 1.74-2.84), respectively. Higher TWA-L ≤500/µL was also independently associated with increased risk, whereas milder lymphopenia (≤1000/µL) showed weaker and inconsistent associations.
Conclusions:
Early sustained deep lymphopenia (ALC ≤ 500/µL), quantified by duration or cumulative burden, identifies patients at increased risk of recurrent sepsis and may support early immune risk stratification.
