{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T09:02:07Z","timestamp":1785315727001,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Objective: Post-Intensive Care Syndrome is a multidimensional sequela of critical illness that includes physical, cognitive, and psychological impairments after intensive care unit discharge. Systemic inflammation has been proposed as one potential mechanism contributing to selected PICS domains, but the direction, timing, and clinical relevance of this relationship remain uncertain. This study assessed whether serial concentrations of C-reactive protein, procalcitonin, and interleukin-6 were associated with PICSQ severity in ICU survivors. Materials and Methods: This prospective single-center cohort study included 267 adult ICU patients in the primary complete case analysis. CRP, PCT, and IL-6 were measured at predefined time points during hospitalization. PICS severity was assessed using the Post-Intensive Care Syndrome Questionnaire at ICU discharge and at 2 and 3 months after discharge. The primary endpoint was total PICSQ severity at 3 months. Correlation analyses, threshold-based group comparisons, and logistic and multivariable linear regression models adjusted for age, sex, reason for ICU admission, and length of hospitalization were performed. Secondary and domain-specific analyses were considered exploratory. Results: Correlation analyses did not show a consistent association between inflammatory biomarkers and total PICSQ severity at ICU discharge, 2 months, or 3 months. Weak inverse associations were observed between selected CRP, PCT, and IL-6 measurements and cognitive domain scores, indicating lower cognitive impairment scores among patients with higher biomarker values in some analyses. These findings were not consistent across time points and should be interpreted cautiously. In unadjusted threshold-based analyses at 3 months, selected associations were observed for CRP after one week, PCT on day 4, and IL-6 on days 2 and 4, mainly in the psychological domain. In fully adjusted linear regression models, none of the selected biomarker thresholds remained statistically significant at p &lt; 0.05. In adjusted linear regression, PCT \u2265 2 ng\/mL on day 4 showed a borderline association with the total PICSQ score at 3 months, with \u03b2 = 0.44, 95% CI \u22120.07 to 0.94, p = 0.089, N = 267. IL-6 &gt; 10 pg\/mL on day 2 showed a borderline association with psychological domain severity at 3 months, with \u03b2 = 0.46, 95% CI from \u22120.005 to 0.92, p = 0.052. In adjusted logistic regression, IL-6 &gt; 10 pg\/mL on day 2 was associated with higher odds of psychological domain score \u2265 4 at 3 months, with adjusted OR 3.61, 95% CI 1.26 to 10.37, p = 0.017, N = 266. No consistent association was observed for the physical domain. Conclusions: In this exploratory cohort, routinely available inflammatory biomarkers were not consistently associated with global PICSQ severity across all assessment time points. Selected time-dependent and domain-specific associations, particularly involving PCT and IL 6 at 3 months, may indicate a possible link between inflammatory activation and later psychological PICS burden. These findings do not establish causality or predictive performance and require external validation before CRP, PCT, or IL 6 can be used for PICS risk stratification.<\/jats:p>","DOI":"10.3390\/diagnostics16152361","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"2361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Biomarkers and Post-Intensive Care Syndrome: A Prospective Cohort Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3094-2385","authenticated-orcid":false,"given":"Mateusz","family":"Szczupak","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy of the Nicolaus Copernicus Hospital in Gda\u0144sk, Nowe Ogrody 1-6 Street, 80-803 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Kobak","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medicine, Medical University of Gda\u0144sk, Sklodowskiewj-Curie 3a Street, 80-210 Gda\u0144sk, Poland"},{"name":"Department of Otolaryngology, University Clinical Center, Mariana Smoluchowskiego 17 Street, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Wierzchowska","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy of the Nicolaus Copernicus Hospital in Gda\u0144sk, Nowe Ogrody 1-6 Street, 80-803 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-0978","authenticated-orcid":false,"given":"Jakub","family":"Wi\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Copernicus Hospital in Gda\u0144sk, Nowe Ogrody 1-6 Street, 80-803 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-6934","authenticated-orcid":false,"given":"Marek","family":"Konop","sequence":"additional","affiliation":[{"name":"Laboratory of the Center for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3002-3153","authenticated-orcid":false,"given":"Sabina","family":"Krupa-Nurcek","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, Collegium Medicum, University of Rzesz\u00f3w, Waclawa Kopisto 2A Street, 35-959 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e929","DOI":"10.1002\/ams2.929","article-title":"Post-intensive care syndrome: Recent advances and future directions","volume":"11","author":"Inoue","year":"2024","journal-title":"Acute Med. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13613-022-01038-0","article-title":"Chronic critical illness and post-intensive care syndrome: From pathophysiology to clinical challenges","volume":"12","author":"Voiriot","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13613-025-01429-z","article-title":"Estimated prevalence of post-intensive care cognitive impairment at short-term and long-term follow-ups: A proportional meta-analysis of observational studies","volume":"15","author":"Ho","year":"2025","journal-title":"Ann. Intensive Care"},{"key":"ref_4","unstructured":"Smith, S., and Rahman, O. (2026, April 26). Postintensive Care Syndrome, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK558964\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1164\/rccm.201904-0816CI","article-title":"Natural History of Cognitive Impairment in Critical Illness Survivors. A Systematic Review","volume":"202","author":"Honarmand","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1001\/jama.2010.1553","article-title":"Long-term cognitive impairment and functional disability among survivors of severe sepsis","volume":"304","author":"Iwashyna","year":"2010","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1097\/CCM.0000000000003218","article-title":"Co-Occurrence of Post-Intensive Care Syndrome Problems Among 406 Survivors of Critical Illness","volume":"46","author":"Marra","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00101-024-01483-5","article-title":"Das Post-Intensive Care Syndrom: Funktionelle Beeintr\u00e4chtigungen bei \u00dcberlebenden kritischer Erkrankung [Post-Intensive Care Syndrome: Functional impairments of critical illness survivors]","volume":"74","author":"Paul","year":"2025","journal-title":"Anaesthesiologie"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4103\/singaporemedj.SMJ-2025-099","article-title":"Post-intensive care syndrome: A state-of-the-art review","volume":"67","author":"Lau","year":"2026","journal-title":"Singap. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1097\/CCM.0000000000004586","article-title":"Society of Critical Care Medicine\u2019s International Consensus Conference on Prediction and Identification of Long-Term Impairments After Critical Illness","volume":"48","author":"Mikkelsen","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1056\/NEJMoa1301372","article-title":"BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness","volume":"369","author":"Pandharipande","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.5935\/2965-2774.20230422-en","article-title":"Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: A prospective cohort study","volume":"35","author":"Rocha","year":"2023","journal-title":"Crit. Care Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s12035-018-1166-x","article-title":"Predicting Long-term Cognitive Dysfunction in Survivors of Critical Illness with Plasma Inflammatory Markers: A Retrospective Cohort Study","volume":"56","author":"Maciel","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1164\/rccm.201912-2449OC","article-title":"Inflammation and Coagulation during Critical Illness and Long-Term Cognitive Impairment and Disability","volume":"203","author":"Brummel","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e825","DOI":"10.1097\/CCM.0000000000003299","article-title":"Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation\/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU","volume":"46","author":"Devlin","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13054-021-03535-3","article-title":"Long-term outcomes after critical illness: Recent insights","volume":"25","author":"Rousseau","year":"2021","journal-title":"Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e31278","DOI":"10.1016\/j.heliyon.2024.e31278","article-title":"Post intensive care syndrome: A review of clinical symptoms, evaluation, intervention","volume":"10","author":"He","year":"2024","journal-title":"Heliyon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/anae.16258","article-title":"Association between inflammation and post-intensive care syndrome: A systematic review","volume":"79","author":"Docherty","year":"2024","journal-title":"Anaesthesia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104370","DOI":"10.1016\/j.jcv.2020.104370","article-title":"Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19","volume":"127","author":"Liu","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_20","first-page":"e3868","article-title":"Evaluation of Serum Interleukin-6 and C-reactive Protein Levels in Drug-na\u00efve Major Depressive Disorder Patients","volume":"11","author":"Nishuty","year":"2019","journal-title":"Cureus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbi.2021.05.022","article-title":"Investigating whether a combination of higher CRP and depression is differentially associated with worse executive functioning in a cohort of 43,896 adults","volume":"96","author":"Alloy","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Buzgau, P., Slevin, M., Barna, I.T., D\u00e9nes, L., Tero-Vescan, A., Russo, A.P., and Pastorello, Y. (2026). C-Reactive Protein and Neurological Autoimmune Diseases: Bridging the Diagnostic and Pathogenic Gap. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031322"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1038\/s41598-024-82992-6","article-title":"Cytokines and inflammatory biomarkers and their association with post-operative delirium: A meta-analysis and systematic review","volume":"15","author":"Mosharaf","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Szczupak, M., Kobak, J., Ingielewicz, A., Wi\u015bniewski, J., and Krupa-Nurcek, S. (2025). The Role of C-Reactive Protein as a Biomarker for Postoperative Delirium Following Cardiac and Neurosurgical Surgery: A Retrospective Analysis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14228252"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rivera-Fernandez, R., Y\u00e1guez-Mateos, L., Guerrero-Marin, M., P\u00e9rez-Manrique, R.M., Rojas-Amezcua, M., Pontes-Moreno, A.J., R\u00edos-Toro, J.J., Vela-Colmenero, R., Ruiz-Garcia, M.I., and Colmenero-Aguilar, C. (2022). Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study. Front Med., 9.","DOI":"10.3389\/fmed.2022.972659"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ajem.2020.11.011","article-title":"Clinical value of procalcitonin in critically ill patients infected by SARS-CoV-2","volume":"46","author":"Garrido","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12931-025-03402-7","article-title":"Persistent systemic interleukin-6 elevation after community-acquired pneumonia is associated with one-year mortality","volume":"26","author":"Piqueras","year":"2025","journal-title":"Respir. Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2361\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:33:13Z","timestamp":1785313993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/15\/2361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":27,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["diagnostics16152361"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16152361","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}