{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:09:24Z","timestamp":1793045364708,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysregulated cytokine responses are a hallmark of severe COVID-19; however, the persistence of these responses following hospital discharge remains inadequately understood. This study aimed to characterize the inflammatory profile of hospitalized COVID-19 patients in Mure\u0219 County, Romania, at the point of admission and one month post-discharge. We conducted a prospective observational study involving 68 patients with RT-PCR-confirmed SARS-CoV-2 infection, classified according to disease severity. Blood samples were collected at baseline and after one month. Macrophage migration inhibitory factor (MIF) levels were quantified using ELISA, while other cytokines, including MCP-1, IP-10, IFN-\u03b3, IL-4, IL-10, IL-13, IL-17, and TNF-\u03b1, were measured via Luminex multiplex assays. Patients with severe disease exhibited significantly elevated levels of MIF, IFN-\u03b3, IL-17, and TNF-\u03b1 at admission (p &lt; 0.0001). Although cytokine concentrations generally declined over time, patients with severe disease continued to display persistently elevated MIF (mean 31,035 pg\/mL), IFN-\u03b3, and TNF-\u03b1, indicative of ongoing inflammatory processes. Clinical parameters such as respiratory rate and oxygen saturation correlated with disease severity. These findings suggest that severe COVID-19 induces a prolonged inflammatory response, with MIF and IFN-\u03b3 remaining elevated beyond the acute phase. Cytokine profiling holds potential for improving prognostic assessments and identifying patients at risk of long-term immune dysregulation, with MIF emerging as a potential candidate marker for immune recovery and a possible target for therapy.<\/jats:p>","DOI":"10.3390\/ijms26199697","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:05:06Z","timestamp":1759763106000},"page":"9697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage Migration Inhibitory Factor and Post-Discharge Inflammatory Profiles in Severe COVID-19: A Prospective Observational Study from Romania"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9298-3185","authenticated-orcid":false,"given":"Nimr\u00f3d","family":"L\u00e1szl\u00f3","sequence":"first","affiliation":[{"name":"Department of Pulmonology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"},{"name":"Doctoral School of Medicine and Pharmacy, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9439-0590","authenticated-orcid":false,"given":"Corina","family":"M\u0103rginean","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-1566","authenticated-orcid":false,"given":"Botond Barna","family":"M\u00e1ty\u00e1s","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"},{"name":"Department of Cardiology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Alexandra","family":"Man","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540139 T\u00e2rgu Mure\u0219, Romania"},{"name":"Department of Biochemistry, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5215-6152","authenticated-orcid":false,"given":"El\u0151d Ern\u0151","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1990-6767","authenticated-orcid":false,"given":"Gabriela","family":"Jimborean","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,5]]},"reference":[{"key":"ref_1","first-page":"70","article-title":"Biomarkers of Systemic Versus Local Inflammation During the Acute Phase of Myocardial Infarction, as Predictors of Post-infarction Heart Failure","volume":"7","author":"Matyas","year":"2021","journal-title":"J. Cardiovasc. Emerg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/22221751.2020.1770129","article-title":"Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors","volume":"9","author":"Han","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","article-title":"A dynamic COVID-19 immune signature includes associations with poor prognosis","volume":"26","author":"Laing","year":"2020","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e137799","DOI":"10.1172\/jci.insight.137799","article-title":"The laboratory tests and host immunity of COVID-19 patients with different severity of illness","volume":"5","author":"Wang","year":"2020","journal-title":"JCI Insight"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.abc6261","article-title":"Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans","volume":"369","author":"Arunachalam","year":"2020","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/mmr.2020.11127","article-title":"Obesity a risk factor for increased COVID-19 prevalence, severity and lethality","volume":"22","author":"Petrakis","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Capraru, I.D., Marian, C., Vulcanescu, D.D., Tanasescu, S., Dragomir, T.L., Marti, T.D., Boru, C., Avram, C.R., Susan, M., and Vlad, C.S. (2024). Understanding the impact of COVID-19 on Roma vulnerable communities in Western Romania: Insights and predictive factors from a retrospective study. Viruses, 16.","DOI":"10.3390\/v16030435"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2478\/rjc-2023-0011","article-title":"Impact of COVID-19 Infection on Regional Periocoronary Inflammation: An Angio-CT Study of Epicardial Fat Attenuation","volume":"33","author":"Benedek","year":"2023","journal-title":"Rom. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"M\u0103rc\u0103u, F.C., Purec, S., and Niculescu, G. (2022). Study on the Refusal of Vaccination against COVID-19 in Romania. Vaccines, 10.","DOI":"10.3390\/vaccines10020261"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Manole, C., Baroiu, L., Nechita, A., Voinescu, D.C., Ciubara, A., Debita, M., Tatu, A.L., Ciubara, A.B., Stefanopol, I.A., and Anghel, L. (2023). Comparative evaluation of the clinical severity of COVID-19 of vaccinated and unvaccinated patients in Southeastern Romania in the first 6 months of 2022, during the Omicron wave. Healthcare, 11.","DOI":"10.3390\/healthcare11152184"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.abb8925","article-title":"Cytokine release syndrome in severe COVID-19","volume":"368","author":"Moore","year":"2020","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Huang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nri1200","article-title":"Macrophage migration inhibitory factor: A regulator of innate immunity","volume":"3","author":"Calandra","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Aharon, A., Avni, B., Louzoun, D., Elias, S., Stepensky, P., Ram, R., Zuckerman, T., Meza-Romera, R., Vandenbark, A.A., and Grisariu, S. (2025). MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1504976"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1080\/14728222.2019.1656718","article-title":"Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus","volume":"23","author":"Bilsborrow","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nm0397-320","article-title":"Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome","volume":"3","author":"Donnelly","year":"1997","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41591-021-01386-7","article-title":"CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer","volume":"27","author":"Bange","year":"2021","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1358\/dnp.2010.23.4.1453629","article-title":"Macrophage migration inhibitory factor (MIF): A promising biomarker","volume":"23","author":"Grieb","year":"2010","journal-title":"Drug News Perspect."},{"key":"ref_21","unstructured":"(2022). Clinical Management of COVID-19: Living Guideline, World Health Organization."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3325\/cmj.2023.64.13","article-title":"The performance of the WHO COVID-19 severity classification, COVID-GRAM, VACO Index, 4C Mortality, and CURB-65 prognostic scores in hospitalized COVID-19 patients: Data on 4014 patients from a tertiary center registry","volume":"64","author":"Durlen","year":"2023","journal-title":"Croat. Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41392-021-00686-1","article-title":"SARS-CoV-2-specific immune response in COVID-19 convalescent individuals","volume":"6","author":"Pan","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41590-021-01113-x","article-title":"Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection","volume":"23","author":"Phetsouphanh","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl. Sci. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cell.2022.01.014","article-title":"Multiple early factors anticipate post-acute COVID-19 sequelae","volume":"185","author":"Su","year":"2022","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijid.2021.07.016","article-title":"Long-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: A monocentric prospective observational cohort study","volume":"109","author":"Darcis","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9697\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:46Z","timestamp":1760717626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,5]]},"references-count":29,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199697"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199697","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,5]]}}}