{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:04:17Z","timestamp":1784311457923,"version":"3.55.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2024A03J0643"],"award-info":[{"award-number":["2024A03J0643"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012909"],"award-info":[{"award-number":["2024A1515012909"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis-induced lymphopenia is associated with adverse outcomes, yet static assessments at a single time point fail to capture the clinical significance of its dynamic evolution, and the effects of the trajectories of lymphopenia on prognosis are to be elucidated in sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study extracted data from the MIMIC-IV (v3.1) database. Adult septic patients with initial lymphopenia (&lt;1.0\u2009\u00d7\u200910\u2079\/L) were included. Group-Based Trajectory Modeling (GBTM) identified lymphocyte count trajectories. Kaplan-Meier analysis with log-rank test was used to visualize survival differences. Multivariable Cox and logistic regression assessed associations between trajectories and 7-day, 28-day, ICU, and in-hospital mortality. Subgroup analyses validated result consistency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1,640 patients were included. GBTM identified 4 distinct lymphocyte count trajectories. Kaplan-Meier analysis revealed that patients in Trajectory 4 (Persistent Low Level, N\u2009=\u2009544, 33.2%), characterized by persistent lymphopenia, had the lowest cumulative 7-day and 28-day survival rates. After multivariable adjustment, Trajectory 4 was independently associated with an increased risk of 28-day mortality [adjusted HR\u2009=\u20091.76, 95% CI: 1.266\u20132.446, P\u2009=\u20090.001], ICU mortality (adjusted OR = 1.831, 95% CI: 1.196\u20132.832, P\u2009=\u20090.006), and in-hospital mortality (adjusted OR = 1.881, 95% CI: 1.298\u20132.767, P\u2009=\u20090.001) compared to Trajectory 1 (Sustained Recovery), and these associations remained robust across all predefined subgroups. In contrast, no significant association was observed between Trajectory 4 and 7-day mortality after full adjustment for confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lymphocyte count Trajectory 4 (Persistent Low Level) in initially lymphopenic sepsis patients is independently associated with late (28-day) but not early (7-day) mortality, as well as worse ICU and hospital outcomes. Failure of lymphopenia to recover by days 3\u20134 may signal a transition to the highest-risk state, suggesting a potential window for immunomodulatory strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353698","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:33:58Z","timestamp":1784309638000},"page":"e0353698","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Failure of early lymphocyte recovery identifies sepsis patients with initial lymphopenia at highest risk for late mortality"],"prefix":"10.1371","volume":"21","author":[{"given":"Binli","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-2487","authenticated-orcid":true,"given":"Huasheng","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"pone.0353698.ref001","first-page":"67","article-title":"Sepsis definition: what\u2019s new #8232;in the treatment guidelines","volume":"61","author":"I Srzi\u0107","year":"2022","journal-title":"Acta Clin Croat"},{"issue":"10219","key":"pone.0353698.ref002","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"KE Rudd","year":"2020","journal-title":"Lancet"},{"issue":"3","key":"pone.0353698.ref003","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S1473-3099(13)70001-X","article-title":"Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach","volume":"13","author":"RS Hotchkiss","year":"2013","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"pone.0353698.ref004","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13054-018-2020-2","article-title":"Lymphocyte subset expression and serum concentrations of PD-1\/PD-L1 in sepsis - 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