Specific Changes of Erythroid Regulators and Hepcidin in Patients Infected by SARS-COV-2

Delaye, Jessy; Alarcan, Hugo; Vallet, Nicolas; Veyrat-Durebex, Charlotte; Bernard, Louis; Hérault, Olivier; Ropert, Martine; Marlet, Julien; Gyan, Emmanuel; Andrés, Christian; Blasco, Hélène; Piver, Éric

doi:10.1136/jim-2021-002270

Cited by 6 publications

(15 citation statements)

References 31 publications

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“…Recently, Peng et al have found higher hepcidin and ferritin levels and lower iron levels in severe COVID-19 patients [ 49 ]. Meanwhile, the report by Delaye et al shows that higher hepcidin levels are critical in patients with COVID-19 compared to in non-COVID-19 patients with similar CRP levels [ 50 ]. Growing evidence has revealed that multisystem inflammatory syndrome associated (MIS-C) with COVID-19 in children shares many clinical features [ 51 ] and inflammatory responses with KD [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

et al. 2022

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Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937–0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD.

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Section: Discussionmentioning

confidence: 99%

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

et al. 2022

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“…Though higher hepcidin level was found in cases than that in controls, the difference was not significant (SMD (95%CI): 0.750 (−0.805, 2.306); Z = 0.95 p for Z = 0.345; I 2 = 96.40%, p for I 2 < 0.001; Table 3, Figure 9). [10,18,20,24] on hepcidin levels in COVID-19 cases and controls. The solid diamond and horizontal line represent the study-specific effect and 95%CI, respectively; the size of the grey square is positively correlated with the weight distributed to each study in the meta-analysis.…”

Section: Tibc Tsat and The Mortality Of Covid-19mentioning

confidence: 99%

“…Previous studies have investigated the relationships among iron, ferritin, hemoglobin, hepcidin, TIBC, TSAT and COVID-19, but their results are conflicting and inconsistent. Most studies about serum iron have shown that lower iron levels are found in more at-risk groups, such as non-survivors compared to survivors [8][9][10][11][12][13], severe disease groups compared to non-severe disease groups [10,[13][14][15][16] and cases to controls [10,[16][17][18][19][20][21], whereas others expressed the opposite results [7,22,23]. In all relevant studies, the hemoglobin levels were found to be lower in severe groups than those in controls [7,10,24] or non-severe groups [22,[25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 97%

“…In all relevant studies, the hemoglobin levels were found to be lower in severe groups than those in controls [7,10,24] or non-severe groups [22,[25][26][27][28][29]. However, in the comparisons between severity [7,10,15,[17][18][19]23,24,[30][31][32][33][34][35][36][37] and mortality [10,30,[38][39][40][41], there was not a consistent numerical magnitude relationship between them. In addition, studies on TIBC [8,10,12,13] and TSAT [8,13] only refer to mortality.…”

Section: Introductionmentioning

confidence: 99%

“…Most of those studies found lower levels in nonsurvivor groups, except for one about TSAT [10]. Lower levels of hepcidin in cases than controls was documented in a study [10], whereas the other studies reported an inverse result [18,20,24]. Unusually, more dangerous groups had higher ferritin levels in almost all relevant comparisons [4,6,[10][11][12][13][14][15][17][18][19][20][21][22][24][25][26][27][28][29][30]32,[34][35][36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

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The Associations of Iron Related Biomarkers with Risk, Clinical Severity and Mortality in SARS-CoV-2 Patients: A Meta-Analysis

Zhou

2022

Nutrients

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly around the world and has led to millions of infections and deaths. Growing evidence indicates that iron metabolism is associated with COVID-19 progression, and iron-related biomarkers have great potential for detecting these diseases. However, the results of previous studies are conflicting, and there is not consistent numerical magnitude relationship between those biomarkers and COVID-19. Thereby, we aimed to integrate the results of current studies and to further explore their relationships through a meta-analysis. We searched peer-reviewed literature in PubMed, Scopus and Web of Science up to 31 May 2022. A random effects model was used for pooling standard mean difference (SMD) and the calculation of the corresponding 95% confidence interval (CI). I2 was used to evaluate heterogeneity among studies. A total of 72 eligible articles were included in the meta-analysis. It was found that the ferritin levels of patients increased with the severity of the disease, whereas their serum iron levels and hemoglobin levels showed opposite trends. In addition, non-survivors had higher ferritin levels (SMD (95%CI): 1.121 (0.854, 1.388); Z = 8.22 p for Z < 0.001; I2 = 95.7%, p for I2 < 0.001), lower serum iron levels (SMD (95%CI): −0.483 (−0.597, −0.368), Z = 8.27, p for Z < 0.001; I2 = 0.9%, p for I2 =0.423) and significantly lower TIBC levels (SMD (95%CI): −0.612 (−0.900, −0.324), Z = 4.16, p for Z < 0.001; I2 = 71%, p for I2 = 0.016) than survivors. This meta-analysis demonstrates that ferritin, serum iron, hemoglobin and total iron banding capacity (TIBC) levels are strongly associated with the risk, severity and mortality of COVID-19, providing strong evidence for their potential in predicting disease occurrence and progression.

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Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients

et al. 2023

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Background Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group. Methods and results Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin. COVID-19 patients had higher serum levels of ferritin than those levels in control group (P < 0.0001). Conversely levels of HIF-1α and HEPH in the COVID-19 group were significantly lower than those of control group (P < 0.0001 for both). An inverse correlation between hephaestin and ferritin as well as between HIF-1α and ferritin was found among all subjects (P < 0.0001), and among COVID-19 patients, but not to statistical significance. Conclusion Levels of hephaestin and HIF-1α were found to be inversely related levels of ferritin across all participants in the study, and to our knowledge this is the first report of hephaestin and HIF-1α as potential markers of iron status. Further studies are needed to corroborate the findings, utilizing a broader range of markers to monitor inflammatory as well as iron status.

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Specific Changes of Erythroid Regulators and Hepcidin in Patients Infected by SARS-COV-2

Cited by 6 publications

References 31 publications

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

The Associations of Iron Related Biomarkers with Risk, Clinical Severity and Mortality in SARS-CoV-2 Patients: A Meta-Analysis

Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients

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