{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:02:08Z","timestamp":1762048928787,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Immunocluster project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 \u00b1 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-\u03b3, interleukin 6 (IL-6), IL-1\u03b2, IL-8, IL-10, soluble IL2-receptor-\u03b1 (sIL2R\u03b1), IP10 and TNF\u03b1. Extensive statistical analyses were performed (correlations, t-tests, ranking tests and tree modeling). The mortality rate was 65\/415 (15.7%) and a negative outcome (death and\/or orotracheal intubation) affected 98\/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg\/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2R\u03b1, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2R\u03b1 and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention.<\/jats:p>","DOI":"10.3390\/ijms23094830","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T22:20:20Z","timestamp":1651098020000},"page":"4830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cytokines from Bench to Bedside: A Retrospective Study Identifies a Definite Panel of Biomarkers to Early Assess the Risk of Negative Outcome in COVID-19 Patients"],"prefix":"10.3390","volume":"23","author":[{"given":"Martina","family":"Fabris","sequence":"first","affiliation":[{"name":"Laboratory of Immunopathology, Institute of Clinical Pathology, Department of Laboratory Medicine, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-0669","authenticated-orcid":false,"given":"Fabio","family":"Del Ben","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica (DAME), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6247-5958","authenticated-orcid":false,"given":"Emanuela","family":"Sozio","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-2710","authenticated-orcid":false,"given":"Antonio Paolo","family":"Beltrami","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Institute of Clinical Pathology, Department of Laboratory Medicine, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Dipartimento di Area Medica (DAME), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-8838","authenticated-orcid":false,"given":"Adriana","family":"Cif\u00f9","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica (DAME), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-8718","authenticated-orcid":false,"given":"Giacomo","family":"Bertolino","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Azienda Ospedaliero-Universitaria di Cagliari, 09042 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-648X","authenticated-orcid":false,"given":"Federica","family":"Caponnetto","sequence":"additional","affiliation":[{"name":"Dipartimento di Area Medica (DAME), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cotrufo","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-6024","authenticated-orcid":false,"given":"Carlo","family":"Tascini","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-4807","authenticated-orcid":false,"given":"Francesco","family":"Curcio","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Institute of Clinical Pathology, Department of Laboratory Medicine, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Dipartimento di Area Medica (DAME), University of Udine, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.24875\/AIDSRev.200001261","article-title":"The Importance of Understanding the Stages of COVID-19 in Treatment and Trials","volume":"23","author":"Griffin","year":"2021","journal-title":"AIDS Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. 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