Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients’ performance: a prospective observational cohort study

• Published in: Respiratory research Vol. 21; no. 1; pp. 276 - 9
• Main Authors: Sonnweber, Thomas, Boehm, Anna, Sahanic, Sabina, Pizzini, Alex, Aichner, Magdalena, Sonnweber, Bettina, Kurz, Katharina, Koppelstätter, Sabine, Haschka, David, Petzer, Verena, Hilbe, Richard, Theurl, Markus, Lehner, Daniela, Nairz, Manfred, Puchner, Bernhard, Luger, Anna, Schwabl, Christoph, Bellmann-Weiler, Rosa, Wöll, Ewald, Widmann, Gerlig, Tancevski, Ivan, Judith-Löffler-Ragg, Weiss, Günter
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.10.2020; BioMed Central; BMC
• Subjects: Adult; Aged; Anemia; Anemia - etiology; Biomarkers; C-reactive protein; C-Reactive Protein - analysis; Cohort analysis; Cohort Studies; Complications and side effects; Computed tomography; Coronavirus Infections - complications; Coronavirus Infections - metabolism; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; Cytokines; Female; Ferritin; Ferritins - blood; Follow-Up Studies; Gene expression; Health aspects; Hepcidin; Homeostasis; Hospital patients; Humans; Hyperferritinemia; Inflammation; Inflammation - etiology; Inflammation - metabolism; Interleukin 6; Interleukin-6 - blood; Interleukins; Iron; Iron - metabolism; Iron deficiency; Iron metabolism disorders; Laboratory tests; Leukocytes (mononuclear); Lung Diseases - etiology; Lung Diseases - metabolism; Lung Diseases - physiopathology; Lungs; Male; Metabolism; Middle Aged; Monocytes - metabolism; Nutrient deficiency; Observational studies; Pandemics; Patients; Peripheral blood mononuclear cells; Physiological aspects; Pneumonia, Viral - complications; Pneumonia, Viral - metabolism; Pneumonia, Viral - physiopathology; Prospective Studies; Risk factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Statistical analysis; Statistics; Tomography, X-Ray Computed; Viral diseases; Austria; COVID-19; Hyperferritinemia; Iron metabolism; SARS-CoV-2; Hepcidin
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-020-01546-2

Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. ClinicalTrials.gov number: NCT04416100.