Study reveals persistent CD3+ T-cell decrease linked to higher mortality in elderly patients with sepsis

A new study published online in the Journal of Intensive Medicine on June 17, 2025, highlights early and dynamic alterations in lymphocyte subsets following sepsis in elderly patients and their association with short-term mortality. Sepsis, a life-threatening organ dysfunction caused by dysregulated host responses to infection, was shown to induce a numerical reduction in lymphocytes and CD3⁺ T-cell counts in octogenarian patients.

In this prospective cohort study, 3,601 consecutive patients in the intensive care unit (ICU) admitted between March 2017 and January 2023 were enrolled. Peripheral blood samples were collected on admission, Day 3, and Day 7 for patients with sepsis, and on enrollment for those without sepsis. Lymphocyte subsets were detected by flow cytometry. The 28-day mortality was analyzed using Kaplan–Meier survival analysis, and Cox regression was used to identify prognostic factors.

Patients were divided into three age groups: adult (18–64 years), old (65–79 years), and octogenarian (≥ 80 years). Among octogenarians, sepsis induced a reduction in lymphocytes (median = 0.653 [interquartile range (IQR): 0.500–1.038] vs. median = 0.840 [IQR: 0.579–1.142] ´ 10⁹/L, P = 0.043) and CD3⁺ T-cell counts (median = 0.461 [IQR: 0.312–0.759] vs. median = 0.590 [IQR: 0.417–0.789] ´ 10⁹/L, P = 0.021).

Kaplan–Meier curves demonstrated that, in both old (P < 0.001) and octogenarian (P = 0.02) groups, patients without CD3⁺ T-cell recovery on Day 3 and Day 7 had the highest mortality, followed by those with late recovery, while the early recovery group had the lowest mortality. Multivariate Cox regression identified age (hazard ratio [HR] = 1.217, 95% confidence interval [CI]: 1.050–1.410, P = 0.009) and CD3⁺ T-cell counts (HR = 0.999, 95% CI: 0.999–1.000, P < 0.001) as independent risk factors for 28-day mortality.

“Our findings support the idea that looking at lymphocyte subtypes can help improve how we use the immune system to guide sepsis treatment in older and very elderly patients,” says Prof. Na Cui, the corresponding author. She also mentions, “In real-world clinical practice, if CD3⁺ T-cells keep dropping, doctors should take notice of the patient’s immune health and consider immunotherapy for older and very elderly patients.”

Highlights

1. Sepsis induced a numerical reduction in lymphocytes and CD3⁺ T-cell counts upon onset of sepsis in octogenarian patients.
2. The persistent decrease of CD3⁺ T-cell counts on Day 3 and Day 7 following sepsis was associated with higher mortality in old and octogenarian patients.
3. Age group and CD3⁺T-cell counts were independent risk factors associated with 28-day mortality in patients with sepsis.

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Reference

DOI: https://doi.org/10.1016/j.jointm.2025.04.002