{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:45:42Z","timestamp":1792093542806,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Anemia and disturbances of iron metabolism are frequently encountered in patients with COVID-19 and associated with an adverse clinical course. We retrospectively analyzed 645 consecutive COVID-19 patients hospitalized at the Innsbruck University Hospital. Pre-existing anemia was associated with increased risk for in-hospital death. We further found that the decline in hemoglobin levels during hospital stay is more pronounced in patients with signs of hyperinflammation upon admission, the latter being associated with a nearly two-fold higher risk for new onset anemia within one week. Anemia prevalence increased from 44.3% upon admission to 87.8% in patients who were still hospitalized after two weeks. A more distinct decrease in hemoglobin levels was observed in subjects with severe disease, and new-onset anemia was associated with a higher risk for ICU admission. Transferrin levels decreased within the first week of hospitalization in all patients, however, a continuous decline was observed in subjects who died. Hemoglobin, ferritin, and transferrin levels normalized in a median of 122 days after discharge from hospital. This study uncovers pre-existing anemia as well as low transferrin concentrations as risk factors for mortality in hospitalized COVID-19 patients, whereas new-onset anemia during hospitalization is a risk factor for ICU admission. Anemia and iron disturbances are mainly driven by COVID-19 associated inflammation, and cure from infection results in resolution of anemia and normalization of dysregulated iron homeostasis.<\/jats:p>","DOI":"10.3390\/metabo11100653","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T10:39:20Z","timestamp":1632739160000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Dynamics in Anemia Development and Dysregulation of Iron Homeostasis in Hospitalized Patients with COVID-19"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7849-2971","authenticated-orcid":false,"given":"Lukas","family":"Lanser","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Robert","family":"Burkert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-111X","authenticated-orcid":false,"given":"Rosa","family":"Bellmann-Weiler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schroll","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Wildner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Fritsche","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-2158","authenticated-orcid":false,"given":"G\u00fcnter","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"140430","DOI":"10.1016\/j.scitotenv.2020.140430","article-title":"Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries","volume":"742","author":"Thu","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S2213-2600(20)30316-7","article-title":"Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: An observational study","volume":"8","author":"Karagiannidis","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_5","unstructured":"World Health Organization (2021, July 11). WHO R&D Blueprint: Novel Coronavirus: Outline of Trial Designs for Experimental Therapeutics, 27 January 2020, Geneva, Switzerland. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/330694."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S1473-3099(20)30243-7","article-title":"Estimates of the severity of coronavirus disease 2019: A model-based analysis","volume":"20","author":"Verity","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","article-title":"Genomewide Association Study of Severe Covid-19 with Respiratory Failure","volume":"383","author":"Ellinghaus","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ijid.2020.07.029","article-title":"Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: A systematic review and meta-analysis","volume":"99","author":"Zhou","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_10","first-page":"ofaa521","article-title":"Neopterin predicts disease severity in hospitalized patients with COVID-19","volume":"8","author":"Lanser","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2665-9913(20)30275-7","article-title":"COVID-19-associated hyperinflammation and escalation of patient care: A retrospective longitudinal cohort study","volume":"2","author":"Manson","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bellmann-Weiler, R., Lanser, L., Barket, R., Rangger, L., Schapfl, A., Schaber, M., Fritsche, G., W\u00f6ll, E., and Weiss, G. (2020). Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082429"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"694083","DOI":"10.3389\/fendo.2021.694083","article-title":"Testosterone Deficiency Is a Risk Factor for Severe COVID-19","volume":"12","author":"Lanser","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-020-2355-0","article-title":"Viral and host factors related to the clinical outcome of COVID-19","volume":"583","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2018-06-856500","article-title":"Anemia of inflammation","volume":"133","author":"Weiss","year":"2019","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10238-020-00679-4","article-title":"Anemia in patients with Covid-19: Pathogenesis and clinical significance","volume":"21","author":"Bergamaschi","year":"2021","journal-title":"Clin. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/trf.16226","article-title":"COVID-19 associated with severe autoimmune hemolytic anemia","volume":"61","author":"Jacobs","year":"2021","journal-title":"Transfusion"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.immuni.2011.01.002","article-title":"Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-\u03baB-inducible immune pathways","volume":"34","author":"Nairz","year":"2011","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nri3863","article-title":"Iron homeostasis in host defence and inflammation","volume":"15","author":"Ganz","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","first-page":"619","article-title":"Impact of bacterial infections on erythropoiesis","volume":"19","author":"Hoffmann","year":"2020","journal-title":"Expert. Rev. Anti. Infect. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.1224577","article-title":"Hepcidin and the iron-infection axis","volume":"338","author":"Drakesmith","year":"2012","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.semcdb.2020.12.005","article-title":"Iron in immune cell function and host defense","volume":"115","author":"Haschka","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1056\/NEJMra041809","article-title":"Anemia of Chronic Disease","volume":"352","author":"Weiss","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1182\/blood-2002-08-2459","article-title":"Cytokine-mediated regulation of iron transport in human monocytic cells","volume":"101","author":"Ludwiczek","year":"2003","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20150787","article-title":"The importance of eukaryotic ferritins in iron handling and cytoprotection","volume":"472","author":"Arosio","year":"2015","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1182\/blood.V99.10.3505","article-title":"Regulation of ferritin genes and protein","volume":"99","author":"Torti","year":"2002","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.celrep.2015.11.005","article-title":"Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1\u03b1 upon LPS Activation in the Presence of Ample Oxygen","volume":"13","author":"Siegert","year":"2015","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E32","DOI":"10.1002\/ajh.26027","article-title":"Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients","volume":"96","author":"Nai","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102537","DOI":"10.1016\/j.autrev.2020.102537","article-title":"The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease","volume":"19","author":"McGonagle","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1182\/blood-2012-05-432906","article-title":"Interferon-\u03b3 impairs proliferation of hematopoietic stem cells in mice","volume":"121","author":"Demirel","year":"2013","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1113\/jphysiol.2010.195057","article-title":"Regulation of erythropoietin production","volume":"589","author":"Jelkmann","year":"2011","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e20201541","DOI":"10.1084\/jem.20201541","article-title":"Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection","volume":"218","author":"Caiado","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1182\/blood.V83.4.911.911","article-title":"Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin","volume":"83","author":"Means","year":"1994","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/art.37958","article-title":"Interferon-\u03b3 mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice","volume":"65","author":"Canna","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103068","DOI":"10.1016\/j.transci.2021.103068","article-title":"Iatrogenic anaemia and transfusion thresholds in ICU patients with COVID-19 disease at a tertiary care hospital","volume":"60","author":"Beverina","year":"2021","journal-title":"Transfus. Apher. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1007\/s00134-010-1794-8","article-title":"Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia","volume":"36","author":"Lasocki","year":"2010","journal-title":"Intensive Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.bbagen.2008.08.006","article-title":"Iron metabolism in the anemia of chronic disease","volume":"1790","author":"Weiss","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1182\/blood-2006-06-028787","article-title":"Suppression of hepcidin during anemia requires erythropoietic activity","volume":"108","author":"Pak","year":"2006","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1182\/blood-2005-08-3364","article-title":"Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease","volume":"107","author":"Theurl","year":"2006","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1532\/LH96.04049","article-title":"Anemia of chronic disease: Pathophysiology and laboratory diagnosis","volume":"11","author":"Thomas","year":"2005","journal-title":"Lab. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100861","DOI":"10.1016\/j.mam.2020.100861","article-title":"The changing landscape of iron deficiency","volume":"75","author":"Camaschella","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tremblay, D., Rapp, J.L., Alpert, N., Lieberman-Cribbin, W., Mascarenhas, J., Taioli, E., and Ghaffari, S. (2021). Mild anemia as a single independent predictor of mortality in patients with COVID-19. EJHaem, 1\u20138.","DOI":"10.1182\/blood-2020-141786"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Al-Jarallah, M., Rajan, R., Saber, A.A., Pan, J., Al-Sultan, A.T., Abdelnaby, H., Alroomi, M., Dashti, R., Aboelhassan, W., and Almutairi, F. (2021). In-hospital mortality in SARS-CoV-2 stratified by hemoglobin levels: A retrospective study. EJHaem, 1\u20135.","DOI":"10.21203\/rs.3.rs-727098\/v1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2018-05-815944","article-title":"Iron deficiency","volume":"133","author":"Camaschella","year":"2019","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1080\/07853890.2020.1867323","article-title":"Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice","volume":"53","author":"Richards","year":"2021","journal-title":"Ann. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2003481","DOI":"10.1183\/13993003.03481-2020","article-title":"Cardiopulmonary recovery after COVID-19: An observational prospective multi-center trial","volume":"57","author":"Sonnweber","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s40560-020-00495-8","article-title":"Linkage of alterations in systemic iron homeostasis to patients\u2019 outcome in sepsis: A prospective study","volume":"8","author":"Brandtner","year":"2020","journal-title":"J. Intensive Care"},{"key":"ref_48","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","author":"Hippchen","year":"2020","journal-title":"Hemasphere"},{"key":"ref_49","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","author":"Shah","year":"2020","journal-title":"Crit. Care"},{"key":"ref_50","unstructured":"World Health Organization (2021, July 11). Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/85839."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:04:49Z","timestamp":1760166289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/10\/653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,25]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["metabo11100653"],"URL":"https:\/\/doi.org\/10.3390\/metabo11100653","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,25]]}}}