{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:35:04Z","timestamp":1768552504008,"version":"3.49.0"},"posted":{"date-parts":[[2021,9,14]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":27,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,9,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Growing evidence indicates a link between iron metabolism and COVID-19 clinical progression, supporting the use of iron and inflammatory parameters as relevant biomarkers to predict patients\u2019 outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. Of these, 127 tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission and, in a subgroup of patients, throughout hospitalization. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into 5 groups according to disease severity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. Conversely, the levels of interleukin(IL)-6 and monocyte chemoattractant protein 1 (MCP1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients but did not correlate with disease severity. Longitudinal determinations of iron and ferritin made in a subgroup of patients (n=23) revealed highly variable results.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in hospitalized acute COVID-19-positive patients. Variation of ferritin with time should be revisited in larger cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:p>COVID-19-positive patients have lower serum iron and higher ferritin than COVID-19-negative patients in variable clinical contexts. Lowest serum iron and highest IL-6 levels at hospital admission associate with the poorest outcomes. Association of serum ferritin with disease progression is debatable.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2021.09.09.21263251","type":"posted-content","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T13:55:41Z","timestamp":1631627741000},"source":"Crossref","is-referenced-by-count":8,"title":["Iron related biomarkers predict disease severity in a cohort of Portuguese adult patients during COVID-19 acute infection"],"prefix":"10.64898","author":[{"given":"Ana C.","family":"Moreira","sequence":"first","affiliation":[]},{"given":"Maria J.","family":"Teles","sequence":"additional","affiliation":[]},{"given":"T\u00e2nia","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Clara M.","family":"Bento","sequence":"additional","affiliation":[]},{"given":"In\u00eas Sim\u00f5es","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o T.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[]},{"given":"Gra\u00e7a","family":"Porto","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Maria Salom\u00e9","family":"Gomes","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2021091602550464000_2021.09.09.21263251v1.1","doi-asserted-by":"publisher","DOI":"10.1172\/jci137244"},{"issue":"11","key":"2021091602550464000_2021.09.09.21263251v1.2","doi-asserted-by":"crossref","first-page":"e695","DOI":"10.1093\/cid\/ciaa1419","article-title":"Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System","volume":"72","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"2","key":"2021091602550464000_2021.09.09.21263251v1.3","doi-asserted-by":"crossref","first-page":"e2061","DOI":"10.1371\/journal.pntd.0002061","article-title":"Iron overload favors the elimination of Leishmania infantum from mouse tissues through interaction with reactive oxygen and nitrogen species","volume":"7","year":"2013","journal-title":"PLoS neglected tropical diseases"},{"key":"2021091602550464000_2021.09.09.21263251v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00612-08"},{"key":"2021091602550464000_2021.09.09.21263251v1.5","doi-asserted-by":"crossref","unstructured":"Gomes, A.C. , et al., Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes. Pharmaceuticals (Basel), 2018. 11(3).","DOI":"10.3390\/ph11030084"},{"issue":"6","key":"2021091602550464000_2021.09.09.21263251v1.6","doi-asserted-by":"crossref","first-page":"e492","DOI":"10.1097\/HS9.0000000000000492","article-title":"Hypoferremia is Associated With Increased Hospitalization and Oxygen Demand in COVID-19 Patients","volume":"4","year":"2020","journal-title":"Hemasphere"},{"issue":"1","key":"2021091602550464000_2021.09.09.21263251v1.7","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13054-020-03051-w","article-title":"Systemic hypoferremia and severity of hypoxemic respiratory failure in COVID-19","volume":"24","year":"2020","journal-title":"Crit Care"},{"issue":"7","key":"2021091602550464000_2021.09.09.21263251v1.8","doi-asserted-by":"crossref","first-page":"ofaa250","DOI":"10.1093\/ofid\/ofaa250","article-title":"Serum Iron Level as a Potential Predictor of Coronavirus Disease 2019 Severity and Mortality: A Retrospective Study","volume":"7","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2021091602550464000_2021.09.09.21263251v1.9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.232124"},{"issue":"1","key":"2021091602550464000_2021.09.09.21263251v1.10","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s12931-020-01546-2","article-title":"Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients\u2019 performance: a prospective observational cohort study","volume":"21","year":"2020","journal-title":"Respir Res"},{"key":"2021091602550464000_2021.09.09.21263251v1.11","first-page":"e926178","article-title":"Increased Serum Levels of Hepcidin and Ferritin Are Associated with Severity of COVID-19","volume":"26","year":"2020","journal-title":"Med Sci Monit"},{"issue":"1","key":"2021091602550464000_2021.09.09.21263251v1.12","first-page":"E32","article-title":"Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients","volume":"96","year":"2021","journal-title":"Am J Hematol"},{"issue":"1","key":"2021091602550464000_2021.09.09.21263251v1.13","doi-asserted-by":"crossref","first-page":"13431","DOI":"10.1038\/s41598-021-92921-6","article-title":"The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19","volume":"11","year":"2021","journal-title":"Sci Rep"},{"issue":"Suppl 1","key":"2021091602550464000_2021.09.09.21263251v1.14","first-page":"142","article-title":"The relationship between serum erythropoietin, hepcidin, and haptoglobin levels with disease severity and other biochemical values in patients with COVID-19","volume":"43","year":"2021","journal-title":"Int J Lab Hematol"},{"issue":"1","key":"2021091602550464000_2021.09.09.21263251v1.15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12967-021-02744-2","article-title":"Combined lymphocyte\/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility","volume":"19","year":"2021","journal-title":"J Transl Med"},{"key":"2021091602550464000_2021.09.09.21263251v1.16","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2020-0369"},{"issue":"5","key":"2021091602550464000_2021.09.09.21263251v1.17","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1016\/j.clnu.2020.11.033","article-title":"Association between iron status and the risk of adverse outcomes in COVID-19","volume":"40","year":"2021","journal-title":"Clinical Nutrition"},{"key":"2021091602550464000_2021.09.09.21263251v1.18","unstructured":"Sa\u00fade, D.-D.G.d. , Prescri\u00e7\u00e3o e determina\u00e7\u00e3o do hemograma. 2011, 2011. 063."},{"issue":"2","key":"2021091602550464000_2021.09.09.21263251v1.19","doi-asserted-by":"crossref","first-page":"80","DOI":"10.20344\/amp.9817","article-title":"Challenges of Ageing in Portugal: Data from the EpiDoC Cohort","volume":"31","year":"2018","journal-title":"Acta Med Port"},{"key":"2021091602550464000_2021.09.09.21263251v1.20","doi-asserted-by":"crossref","unstructured":"Mathew, D. , et al., Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. 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