First-week absolute lymphocyte count dynamics and 28-day mortality in older adults with sepsis

Sepsis is a syndrome in which immune recovery is impaired and the clinical course becomes more severe, particularly in older patients. Although lymphopenia is an easily monitored indicator of sepsis-associated immune dysfunction, the clinical significance of daily lymphocyte changes during the first week in older intensive care patients remains unclear. This study evaluated associations between absolute lymphocyte count (ALC) dynamics, 28-day mortality, and a culture-based secondary microbiological outcome in patients aged ≥ 65 years with sepsis.

In this single-center retrospective cohort, patients aged ≥ 65 years admitted from the emergency department to the ICU with sepsis between January 1, 2022 and December 31, 2025 were included. Daily ALC during days 1-7 was categorized as no lymphopenia (≥ 1000 cells/mm³), moderate lymphopenia (500-999 cells/mm³), or severe lymphopenia (< 500 cells/mm³). The primary outcome was 28-day all-cause mortality; the secondary outcome was 28-day nosocomial culture positivity.

Among 566 patients, the mean age was 80.7 ± 8.0 years, 48.2% were female, and 28-day mortality was 41.0%. ALC was available for all patients through ICU day 3 and for 514/566 patients (90.8%) on ICU day 7; later non-availability reflected shortened observation time rather than random laboratory omission. Severe lymphopenia declined from 33.9% on day 1 to 24.7% on day 7. Mortality was highest in severe lymphopenia, with FDR-corrected significance on day 2 and days 4-7. In the prespecified day-4 multivariable model, severe lymphopenia was independently associated with mortality (aOR 1.84, 95% CI 1.08-3.14; p = 0.025), whereas moderate lymphopenia was not. Increasing severe-lymphopenia burden was also associated with mortality during days 1-4 (aOR 1.16; p = 0.033) and days 1-7 (aOR 1.13; p = 0.013). Nosocomial culture positivity showed unadjusted late-week associations, but not after adjustment.

In older ICU patients with sepsis, day-4 severe lymphopenia and first-week severe-lymphopenia burden were associated with 28-day mortality. The culture-based secondary outcome was not confirmed after adjustment and should be considered exploratory. First-week ALC monitoring may aid bedside risk stratification, but prospective multicenter validation is needed.