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1.
Sci Rep ; 11(1): 19618, 2021 10 04.
Article in English | MEDLINE | ID: covidwho-1450293

ABSTRACT

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.


Subject(s)
COVID-19/pathology , Iron/blood , Adult , Aged , COVID-19/mortality , COVID-19/virology , Cross-Sectional Studies , Female , Ferritins/blood , Ferritins/metabolism , Hepcidins/blood , Hepcidins/metabolism , Hospital Mortality , Humans , Iron/chemistry , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferrin/chemistry , Transferrin/metabolism
2.
Nutrients ; 13(2)2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1218624

ABSTRACT

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.


Subject(s)
Anemia/complications , Iron/blood , Life Style , Neoplasms/complications , Anemia/blood , Anemia, Iron-Deficiency/blood , Animals , COVID-19 , Diet , Food, Fortified , Gastrointestinal Microbiome , Hepcidins/blood , Homeostasis , Humans , Inflammation/blood , Liver/metabolism , Muscle, Skeletal
3.
Int J Lab Hematol ; 43 Suppl 1: 142-151, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1069396

ABSTRACT

INTRODUCTION: Studies have shown that iron metabolism is affected by coronavirus disease 19 (COVID-19), which has spread worldwide and has become a global health problem. Our study aimed to evaluate the relationship between COVID-19 and serum erythropoietin (EPO), hepcidin, and haptoglobin (Hpt) levels with disease severity, and other biochemical values. METHODS: Fifty nine COVID-19 patients hospitalized in the intensive care unit (ICU) and wards in our hospital between March and June 2020 and 19 healthy volunteers were included in the study. Participants were divided into mild, severe, and critical disease severity groups. Group mean values were analyzed with SPSS according to disease severity, mortality, and intubation status. RESULTS: Hemoglobin (Hb) levels were significantly lower in the critical patient group (P < .0001) and deceased group (P < .0001). The red blood cell distribution width-coefficient of variation (RDW-CV) and ferritin values were significantly higher in the intubated (P = .001, P = .005) and deceased (P = .014, P = .003) groups. Ferritin values were positively correlated with disease severity (P < .0001). Serum iron levels were lower in the patient group compared with the reference range. (P < .0001). It was found that the transferrin saturation (TfSat) was lower in the patient group compared with the control group (P < .0001). It was found that the mean EPO of the deceased was lower than the control group and the survived patient group (P = .035). Hepcidin levels were found to be significantly lower in the patient group (P < .0001). Hpt values were found to be significantly lower in the intubated group (P = .004) and the deceased group (P = .042). CONCLUSION: In our study, while serum iron and hepcidin levels decreased in patients diagnosed with COVID-19, we found that EPO and Hpt levels were significantly lower in critical and deceased patient groups. Our study is the first study examining EPO and Hpt levels in patients diagnosed with COVID-19.


Subject(s)
COVID-19/blood , Erythropoietin/blood , Haptoglobins/analysis , Hepcidins/blood , SARS-CoV-2 , Aged , Biomarkers , Cross-Sectional Studies , Female , Ferritins/blood , Hemoglobins/analysis , Homeostasis , Humans , Intubation, Intratracheal/statistics & numerical data , Iron/blood , Male , Middle Aged , Severity of Illness Index , Transferrin/analysis
5.
Med Sci Monit ; 26: e926178, 2020 Sep 26.
Article in English | MEDLINE | ID: covidwho-796300

ABSTRACT

BACKGROUND The aim of this study was to assess the diagnostic utility of iron homeostasis determinations for prediction of severity of COVID-19. MATERIAL AND METHODS This was a retrospective study enrolling a total of 50 patients diagnosed with the novel coronavirus disease-19 (COVID-19) from February 27, 2020 to March 30, 2020, including a severe group (12 patients) and a mild group (38 patients). For the control group, 50 healthy people were examined during the same period. We compared clinical laboratory data and iron homeostasis biomarkers among the 3 groups. ROC curve analysis was used to assess diagnoses. RESULTS Patients diagnosed with severe COVID-19 had higher hepcidin and serum ferritin levels than in other groups (p<0.001). A combination test of hepcidin and serum ferritin provided the best specificity and sensitivity in the prognosis of COVID-19 severity. Logistic regression analysis showed hepcidin and serum ferritin independently contributed to the severity of COVID-19. Hepcidin and serum ferritin tandem testing predicted COVID-19 severity with 94.6% specificity, while hepcidin and serum ferritin parallel testing had a sensitivity of 95.7%. CONCLUSIONS Iron homeostasis had a robust association with the occurrence of severe COVID-19. Iron homeostasis determinations were specific and sensitive for the early prediction of disease severity in COVID-19 patients and thus have clinical utility.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Ferritins/blood , Hepcidins/blood , Pandemics , Pneumonia, Viral/blood , Adult , Aged , Area Under Curve , Biomarkers , COVID-19 , Female , Homeostasis , Humans , Iron/metabolism , Logistic Models , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity
6.
Eur J Epidemiol ; 35(8): 763-773, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-725658

ABSTRACT

Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 1012 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.


Subject(s)
Anemia/diagnosis , Coronavirus Infections , Coronavirus/metabolism , Iron/metabolism , Pandemics , Pneumonia, Viral , Betacoronavirus , Biomarkers/analysis , Biomarkers/blood , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Erythropoietin , Ferritins/blood , Hemoglobins/analysis , Hemoglobins/metabolism , Hepcidins/blood , Hepcidins/metabolism , Humans , Iron/blood , Pneumonia, Viral/epidemiology , Receptors, Transferrin/blood , SARS-CoV-2 , Transferrin/analysis , Transferrin/metabolism
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