Enhanced insights into immunity traits of elderly patients in the intensive care unit with infections: evidence from a multicenter, prospective observational study

Abstract

Infections, particularly sepsis, are a global health threat and a leading cause of mortality among elderly patients (≥ 60 years) in intensive care units (ICUs). The variable immune responses in this vulnerable population warrant deeper investigation. This multicenter prospective study included elderly patients with infections admitted to the ICUs of four hospitals between May 2023 and October 2024. Patients were classified into sepsis and non-sepsis infection groups based on a ≥2-point increase in Sequential Organ Failure Assessment (SOFA) score. Baseline immune and inflammatory markers were compared between groups. Logistic regression analyses were used to assess associations with mortality. Subgroup analyses were conducted by sex, age, infection site, and pathogen type. Among 1,152 elderly patients with infections in the ICUs, 640 with sepsis were older (70.0 vs.72.0 years), were predominantly male (55.3% vs. 68.1%), and had more comorbidities, all P < 0.001. Compared with the non-sepsis infection group, the septic group had higher rates of mechanical ventilation (3.12% vs. 40.80%), longer hospitalization (7.00 [4.00;10.0] vs. 11.8 [6.00;18.0] days), and increased mortality (0.98% vs. 9.51%), all P < 0.001. Distinct immune-mortality signatures were observed. In the fully adjusted model, non-septic infection was associated with reduced monocytes, lymphocytes, and TNFα (odds ratio [OR] < 1), elevated interleukin-12 (IL12) and INFγ (OR > 1, all P < 0.05), whereas sepsis was characterized by increased neutrophil and B-cell activation (OR > 1), decreased T cells (OR < 1, all P < 0.05), and no specific cytokine signature (all P > 0.05). Sex differences included higher levels of innate immune markers in males and elevated adaptive immune indicators in females. With age, patients showed reduced T cell counts and increased inflammatory markers (procalcitonin and C-reactive protein). Patients aged > 80 years exhibited marked lymphopenia, lower CD4+ T cell counts (β < 1, P < 0.05), and elevated IL6 and platelet levels (β > 1, P < 0.05). Immune profiles also varied by pathogen type: fungal infections were associated with increased lymphocyte and cytotoxic T lymphocyte counts (β > 1, P < 0.05) compared with bacterial infections, whereas viral infections showed reduced T cell subsets and cytokine levels (IL6, IL8, IL17; β < 1, P < 0.05). Elderly patients in the ICU, especially those with sepsis, exhibit immune imbalances of hyperinflammation and immunosuppression, varying with age, sex, pathogen type, and infection site. These findings highlight the potential role of immune phenotyping in guiding treatment decisions in this patient population.