Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis

Abstract

Background: Sepsis induces profound derangements in the immune system, including lymphopenia, which correlates with immunosuppression and poor prognosis. However, most evaluations of immunosuppression in sepsis patients rely on static, sporadic lymphocyte counts, lacking dynamic modeling over the disease course. This study aimed to apply latent class mixed modeling on longitudinal lymphocyte counts to uncover heterogeneous trajectory phenotypes in sepsis patients and assess their predictive value for clinical outcomes. Results: Four lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high–declining (α, 3.8%), stable–medium (β, 69.3%), high–increasing (γ, 3.2%), and stable–low (δ, 23.8%). The α phenotype exhibited the highest disease severity and mortality (25.9%) compared with other phenotypes in both cohorts. In the prospective cohort (n=1,056), all lymphocyte subset counts differed among phenotypes on admission (P