Covidin, a possible new player between hepcidin and ferroportin in hypoxia and inflammation caused by COVID‐19

Biasiotto, Giorgio; Ferrari, Fabiana

doi:10.1002/jcb.30246

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…Consequently, replete iron stores and inflammation increase hepcidin production, while iron shortage and increased erythropoiesis inhibit its expression. Additionally, IL-6 and other inflammatory cytokines induce the expression of hepcidin by the pathway JAK2/STAT3, causing anemia of inflammation [36,37].…”

Section: Discussionmentioning

confidence: 99%

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

Ferrari,

Carini,

Zanella

et al. 2024

Diagnostics

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Background: Anemia is the main extraintestinal comorbidity of Inflammatory Bowel Disease (IBD). Differentiating the type of anemia in these disorders is still a challenge. Hepcidin could be a promising biomarker to identify iron deficiency anemia (IDA), anemia of chronic disease (ACD) and the concomitant presence of both IDA and ACD. Methods: To evaluate the potential role of hepcidin dosage in the management of anemia in IBD patients, we performed a systematic review by a comprehensive literature analysis of original papers reporting the dosage of hepcidin in IBD patients. In all the articles reviewed, the dosage of ferritin was reported, and the correlation between hepcidin and ferritin has been used to compare these two biomarkers. Results: A total of 12 articles concerning the dosage of hepcidin in IBD were included, comprising in total of 976 patients. The results of the hepcidin values in IBD patients when compared with controls were conflicting. In fact, four articles described an increase in this biomarker, three showed a decrease and five did not find significant differences. The correlation with ferritin was positive and significant. In three studies, some differences between hepcidin dosages and ferritin levels indicate a possible role when IDA and ACD could be present at the same time. Conclusions: Considering the contradictory data of the studies, the diagnostic role of hepcidin as a biomarker remains elusive in IBD patients. These differences could be due to the clinical characteristics of the patients enrolled that should be better defined in the future. A suitable clinical trial should be designed to outline the possible role of hepcidin in differentiating IDA, ACD and concomitant IDA and ACD in IBD patients. At the moment, ferritin still remains the best marker to diagnose these conditions, in addition to hemoglobin, transferrin saturation and CRP as recommended by the ECCO guidelines.

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Section: Discussionmentioning

confidence: 99%

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

Ferrari,

Carini,

Zanella

et al. 2024

Diagnostics

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“…This effect has been observed at least during HBV, HCV (hepatitis C virus), HIV-1, and HCMV infections [ 61 ]. In fact, the pandemic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) encodes its own hepcidin homologous protein, the covidin protein [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus Infection Is Associated with Elevated Hepcidin Levels

Duque

Mendoza

Morán

et al. 2023

IJMS

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EBV and Helicobacter pylori (H. pylori) cause highly prevalent persistent infections as early as in childhood. Both pathogens are associated with gastric carcinogenesis. H. pylori interferes with iron metabolism, enhancing the synthesis of acute-phase proteins hepcidin, C-reactive protein (CRP), and α-1 glycoprotein (AGP), but we do not know whether EBV does the same. In this study, we correlated the EBV antibody levels and the serum levels of hepcidin, CRP, and AGP in 145 children from boarding schools in Mexico City. We found that children IgG positive to EBV antigens (VCA, EBNA1, and EA) presented hepcidin, AGP, and CRP levels higher than uninfected children. Hepcidin and AGP remained high in children solely infected with EBV, while CRP was only significantly high in coinfected children. We observed positive correlations between hepcidin and EBV IgG antibodies (p < 0.5). Using the TCGA gastric cancer database, we also observed an association between EBV and hepcidin upregulation. The TCGA database also allowed us to analyze the two important pathways controlling hepcidin expression, BMP–SMAD and IL-1β/IL-6. We observed only the IL-1β/IL-6-dependent inflammatory pathway being significantly associated with EBV infection. We showed here for the first time an association between EBV and enhanced levels of hepcidin. Further studies should consider EBV when evaluating iron metabolism and anemia, and whether in the long run this is an important mechanism of undernourishment and EBV gastric carcinogenesis.

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“…COVID-19 is often associated with a 'cytokine storm' and the life threatening, acute respiratory distress syndrome (ARDS). The severity of COVID-19 is influenced by a range of comorbidities [4][5][6], with a large body of literature suggesting that iron deficiency and iron overload may also contribute to disease severity [7][8][9][10][11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…A number of publications have speculated on a connection between iron overload and increased severity of COVID-19, largely based on iron biomarker studies [9,[13][14][15][16][17][18]. In addition, iron loaded mice, injected with a pseudovirus dislaying the spike protein, showed an increase in serum CCL4, IL1β, IL-6 and TNFα levels [8].…”

Section: Introductionmentioning

confidence: 99%

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

Carolin,

Frazer,

Yan

et al. 2024

Preprint

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The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6J mice by feeding low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary omicron XXB SARS-CoV-2 isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.Author summaryA diet deficient in iron can lead to anemia, a widespread problem worldwide. A diet with excessive iron is less common, but can be associated with excessive consumption of iron supplements. We investigate herein using a mouse model, whether low or high iron diets predispose to detrimental outcomes in the lungs after infection with SARS-CoV-2. A considerable literature suggests iron dysregulation would promote infection and inflammation. However, we found, although inflammatory responses showed modest modulations, viral loads were unaffected or slightly reduced, and lung histopathology was either unaffected or indicated slightly less severe disease. These findings do not support a view that low or high iron diets represent comorbidities predisposing to overt detrimental outcomes for acute COVID-19 lung disease.

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Covidin, a possible new player between hepcidin and ferroportin in hypoxia and inflammation caused by COVID‐19

Cited by 3 publications

References 9 publications

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

Epstein–Barr Virus Infection Is Associated with Elevated Hepcidin Levels

The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

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