Early Immunoparalysis Was Associated with Poor Prognosis in Elderly Patients with Sepsis: Secondary Analysis of the ETASS Study

Fei Pei; Guan-Rong Zhang; Li-Xin Zhou; Ji-Yun Liu; Gang Ma; Qiu-Ye Kou; Zhi-Jie He; Min-Ying Chen; Yao Nie; Jian-Feng Wu; Xiang-Dong Guan; China Critical Care Immunotherapy Research Group

doi:10.2147/IDR.S246513

Early Immunoparalysis Was Associated with Poor Prognosis in Elderly Patients with Sepsis: Secondary Analysis of the ETASS Study

Infect Drug Resist. 2020 Jun 30:13:2053-2061. doi: 10.2147/IDR.S246513. eCollection 2020.

Authors

Fei Pei^#^{1

2}, Guan-Rong Zhang^#³, Li-Xin Zhou⁴, Ji-Yun Liu⁵, Gang Ma⁶, Qiu-Ye Kou⁷, Zhi-Jie He⁸, Min-Ying Chen¹, Yao Nie¹, Jian-Feng Wu^{1

2}, Xiang-Dong Guan¹; China Critical Care Immunotherapy Research Group

Affiliations

¹ Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
² Clinical Trial Unit, The First Affiliated Hospital, Sun Yat-sen University & The University of Birmingham, Guangzhou 510080, People's Republic of China.
³ Information and Statistics Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China.
⁴ Department of Critical Care Medicine, Foshan First Municipal People's Hospital, Foshan 528000, People's Republic of China.
⁵ Department of Critical Care Medicine, Guangzhou First Municipal People's Hospital, Guangzhou 510180, People's Republic of China.
⁶ Department of Critical Care Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, People's Republic of China.
⁷ Department of Critical Care Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, People's Republic of China.
⁸ Department of Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality.

Patients and methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome.

Results: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes.

Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

Keywords: early immune status; elderly; immunoparalysis; immunosuppression; mHLA-DR; sepsis.

Grants and funding

This work was funded by Sun Yat-sen University Clinical Research Program 5010 (2007015, XD Guan), Fundamental Research Funds for the Central Universities (15ykpy14, JF Wu), Natural Science Foundation of Guangdong Province (2016A030313269, JF Wu), and Scientific Research Funds of AESCULAP Academy (K0601288, JF Wu).