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.

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Journal
Critical Care Medicine
Published
2026-11-09
DOI
https://doi.org/10.1097/ccm.0000000000007375
Primary Topic
Sepsis Diagnosis and Treatment
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article
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article

Association Between the Neutrophil:Lymphocyte Ratio After Hospitalization for Sepsis and Long-Term Outcomes: A Population-Based Cohort Study

Jacob Colin Jentzer, Edy Yong Kim, Gabriele Lileikyte, Dennis T. Ko et al.
Critical Care Medicine
Sepsis Diagnosis and Treatment
article

Association Between the Neutrophil:Lymphocyte Ratio After Hospitalization for Sepsis and Long-Term Outcomes: A Population-Based Cohort Study

Jacob Colin Jentzer, Edy Yong Kim, Gabriele Lileikyte, Dennis T. Ko, Manu Shankar‐Hari, David E. Leaf, Lucas C. Godoy, James A. Russell, Peter C. Austin, Patrick R. Lawler, Sylvain Lother, Leah B. Kosyakovsky, Michael E. Farkouh, Ryan Zarychanski, Alisa M. Higgins, Alice S. Chong, Cristina Pop, Rebecca Marlene Baron, Michael Chaim Sklar, Guillaume Butler‐Laporte, Fernando Godinho Zampieri, Damon C. Scales, Olivia Haldenby, John C. Marshall, Derek Angus, Lucas L. Marinho, Federico Angriman
article en

Abstract

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.

Critical Care Medicine
Brigham and Women's Hospital (US), St. Michael's Hospital (CA), Beth Israel Deaconess Medical Center (US), Mayo Clinic (US), Harvard University (US), University of British Columbia (CA), University of Alberta (CA), University of Pittsburgh (US), King's College London (GB), University of Toronto (CA), Lund University (SE), McGill University Health Centre (CA), Cedars-Sinai Smidt Heart Institute (US), Sunnybrook Hospital (CA), Ottawa Heart Institute (CA), University of Manitoba (CA), Monash University (AU)
Sepsis Diagnosis and Treatment
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