Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status

Fei Pei; Wenliang Song; Luhao Wang; Liqun Liang; Bin Gu; Minying Chen; Yao Nie; Yishan Liu; Yu Zhou; Xiangdong Guan; Jianfeng Wu

doi:10.3389/fmed.2022.953103

Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status

Front Med (Lausanne). 2022 Aug 4:9:953103. doi: 10.3389/fmed.2022.953103. eCollection 2022.

Authors

Fei Pei^{1

2}, Wenliang Song^{1

2}, Luhao Wang^{1

2}, Liqun Liang^{1

2}, Bin Gu^{1

2}, Minying Chen^{1

2}, Yao Nie^{1

2}, Yishan Liu^{1

2}, Yu Zhou^{1

2}, Xiangdong Guan^{1

2}, Jianfeng Wu^{1

2

3}

Affiliations

¹ Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Clinical Research Center for Critical Care Medicine, Guangzhou, China.
³ Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Background: Immunosuppression is a risk factor for poor prognosis of critically ill patients, but current monitoring of the immune status in clinical practice is still inadequate. Absolute lymphocyte count (ALC) is not only a convenient biomarker for immune status monitoring but is also suitable for clinical application. In this study, we aimed to explore different trajectories of ALC, and evaluate their relationship with prognosis in critically ill patients.

Methods: We retrospectively enrolled 10,619 critically ill patients admitted to a general intensive care unit (ICU) with 56 beds from February 2016 to May 2020. Dynamic ALC was defined as continuous ALC from before ICU admission to 5 days after ICU admission. Initial ALC was defined as the minimum ALC within 48 h after ICU admission. Group-based trajectory modeling (GBTM) was used to group critically ill patients according to dynamic ALC. Multivariate cox regression model was used to determine the independent association of trajectory endotypes with death and persistent inflammation, immunosuppression, catabolism syndrome (PICS).

Results: A total of 2022 critically ill patients were unsupervisedly divided into four endotypes based on dynamic ALC, including persistent lymphopenia endotype (n = 1,211; 58.5%), slowly rising endotype (n = 443; 22.6%), rapidly decreasing endotype (n = 281; 14.5%) and normal fluctuation endotype (n = 87; 4.4%). Among the four trajectory endotypes, the persistent lymphopenia endotype had the highest incidence of PICS (24.9%), hospital mortality (14.5%) and 28-day mortality (10.8%). In multivariate cox regression model, persistent lymphopenia was associated with increased risk of 28-day mortality (HR: 1.54; 95% CI: 1.06-2.23), hospital mortality (HR: 1.66; 95% CI: 1.20-2.29) and PICS (HR: 1.79; 95% CI: 1.09-2.94), respectively. Sensitivity analysis further confirmed that the ALC trajectory model of non-infected patients and non-elderly patients can accurately distinguished 91 and 90% of critically ill patients into the same endotypes as the original model, respectively.

Conclusion: The ALC trajectory model is helpful for grouping critically ill patients, and early persistent lymphopenia is associated with poor prognosis. Notably, persistent lymphopenia may be a robust signal of immunosuppression in critically ill patients.

Keywords: critically ill patient; immunosuppression; lymphocyte (LYM); lymphopenia; persistent inflammation immunosuppression and catabolism syndrome.