Introduction: Immunocompromise significantly increases infection risk. Post-infection, immune dysfunction further worsens clinical status and prognosis. Although older adults bear the highest burden of infections and related mortality, research specifically characterizing pre- and post-infection immune changes in this population remains scarce.
Methods: This is a multicenter, prospective, observational study. We enrolled 1,851 participants (≥60 years) categorized into healthy controls (n=524), nonsevere infection (n=511), and sepsis (n=816) groups. We compared immune and inflammatory biomarker differences across the three participant groups and evaluated their temporal dynamics in severe infection patients at enrollment days 1, 3, and 7. Furthermore, we contrasted these biomarker changes between healthy and the early, severe, and recovery phases of infection.
Results: Significant immune dysregulation in older adults was both age- and severity-dependent. Sepsis patients had more comorbidities and more pronounced routine lab abnormalities (elevated WBC, neutrophils, liver/kidney/coagulation markers; decreased RBC, lymphocytes, albumin) compared to healthy controls and non-severe groups. Lymphocyte counts were severely depleted, especially NK cells (progressively declining to 78 cells/μL in sepsis). Cytokines (IL-6, IL-8, IL-10) increased significantly with both severity and age. While healthy aging featured declining B cells and rising NK cells/cytokines, sepsis caused age-dependent decreases in T cell percentages and increases in NK cells. Longitudinally, survivors maintained higher lymphocyte/T/NK cells, while non-survivors showed persistent inflammation. During phase of recovmery, most biomarkers did not normalize to healthy baselines.Interestingly, the percentage of T/CD8(+) T cells showed a significant peak during this phase.
Conclusions: Older adults exhibit distinct immune functional states across different age groups. Those who develop sepsis display pronounced immunological imbalance, characterized by concurrent hyperinflammation and immunosuppression. The duration of this imbalance correlates negatively with clinical outcomes, and even among survivors, functional immune restoration often fails to reach early infection or healthy baseline levels.
