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While elevated NLR has been shown to predict poor short-term outcomes in patients with COVID-19, its long-term prognostic role\u2014particularly in older adults and in a sex-specific perspective\u2014remains unclear. The aim of this study was to examine the association between admission NLR and 3.5-year all-cause mortality in older adults hospitalised with COVID-19, with a focus on sex-specific patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective observational cohort study with 3.5-year follow-up. A total of 440 patients aged\u2009\u2265\u200965 years hospitalized with confirmed SARS-CoV-2 infection were enrolled. NLR was calculated at admission and dichotomized using the optimal cut-off value (12.63) identified via maximally selected rank statistics. Associations between NLR and mortality were assessed using Cox proportional hazards models, adjusted for age, sex, and vaccination status. Effect modification by sex was explored through interaction terms and sex-stratified analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High NLR at hospital admission was independently associated with an increased risk of long-term all-cause mortality (adjusted HR 1.71; 95% CI: 1.21\u20132.43;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In sex-stratified analyses, this association remained significant only in females (HR 2.50; 95% CI: 1.49\u20134.22;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Sensitivity analyses revealed a significant association for mortality within 90 days of admission (HR 1.80; 95% CI: 1.15\u20132.81;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010), whereas no association was found for deaths occurring beyond 90 days (HR 0.83; 95% CI: 0.43\u20131.61;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.58).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NLR identifies a time-limited window of high vulnerability in older adults, particularly among women, reflecting the interplay between acute inflammation, immunosenescence, and processes typically associated with frailty. These findings highlight NLR as a pragmatic marker of inflammaging that could support sex-sensitive risk stratification and post-discharge interventions in geriatric care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12979-025-00548-2","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T17:16:45Z","timestamp":1767028605000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability"],"prefix":"10.1186","volume":"22","author":[{"given":"Chiara","family":"Ceolin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Liberati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Acunto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Vergadoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Simonato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cazzavillan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Virgilio","family":"Papa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Salerno Trapella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Micael","family":"Zanforlini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Curreri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bertocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gasparini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Devita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Coin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Simioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Sergi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"De Rui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"548_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.smim.2018.09.003","volume":"40","author":"T Fulop","year":"2018","unstructured":"Fulop T, Witkowski JM, Olivieri F, Larbi A. 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The protocol was approved by the local ethics committee (Comitato Etico per la Sperimentazione Clinica della Provincia di Padova; protocol number 16412\/AO\/23), and written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"55"}}