Association between the neutrophil:lymphocyte ratio after hospitalization for sepsis and long-term outcomes: a population-based cohort study

Objectives — Long-term outcomes after sepsis survival remain poor. No clinical laboratory tests are in use for stratifying long-term risk after sepsis, limiting the development of secondary prevention. The peripheral blood neutrophil:lymphocyte ratio (NLR) reflects innate and adaptive immune cell balance, and may reflect an immune milieu which is associated with long-term risk after sepsis. Accordingly, we evaluated the association between the NLR in the weeks after sepsis hospitalization discharge—a time when patients are routinely seen in post-ICU clinics—and long-term outcomes.

Design — Population-based cohort study.

Setting — Ontario, Canada, 2010–2020.

Patients — Adults discharged alive from a sepsis hospitalization.

Interventions — None.

Measurements and main results — The exposure was the first outpatient NLR—derived from the complete blood count—measured 15–90 days after sepsis discharge. Among 37,250 survivors with available NLR, the median (interquartile range [IQR]) time-to-measurement was 34 days (22–54 d), and the median NLR was 2.7 (1.8–4.2). Within 1 year, 17,732 patients (47.6%) were rehospitalized or died (median [IQR] time-to-event, 82 d [27–185 d]). The frequency of rehospitalization or death increased across increasing NLR quartiles: 34.2%, 41.5%, 50.3%, and 64.4% (ptrend < 0.001). Compared with the lowest quartile, adjusted hazard ratios (95% CI) were 1.24 (1.18–1.29), 1.54 (1.48–1.62), and 2.25 (2.15–2.35) across higher quartiles. For most patients, NLR after sepsis returned to its patient-specific presepsis ambient level, which was itself prognostic.

Conclusions — Among sepsis survivors, outpatient NLR measured 15–90 days after discharge is strongly associated with 1-year risk of rehospitalization or death. As a simple, widely available biomarker, the NLR may support early postsepsis risk stratification and inform development of secondary prevention strategies.