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Specific changes of erythroid regulators and hepcidin in patients infected by SARS-COV-2
  1. Jean-Baptiste Delaye1,
  2. Hugo Alarcan1,
  3. Nicolas Vallet2,
  4. Charlotte Veyrat-Durebex1,3,
  5. Louis Bernard4,
  6. Olivier Hérault5,6,
  7. Martine Ropert7,
  8. Julien Marlet8,9,
  9. Emmanuel Gyan2,6,
  10. Christian Andres1,3,
  11. Hélène Blasco1,3,
  12. Eric Piver1,8
  1. 1 Service de Biochimie et Biologie Moléculaire, CHRU Tours, Tours, France
  2. 2 Service d'Hématologie et thérapie cellulaire, CHRU Tours, Tours, France
  3. 3 UMR 1253, iBrain, Université de Tours, Tours, France
  4. 4 Service de Médecine Interne et Maladies Infectieuses, CHRU Tours, Tours, France
  5. 5 Service d'Hématologie biologique, CHRU Tours, Tours, France
  6. 6 CNRS ERL7001 LNOX, EA 3549, Université de Tours, Tours, France
  7. 7 Service de Biochimie, CHU Rennes, Rennes, France
  8. 8 INSERM U1259, MAVIVH, Université de Tours, Tours, France
  9. 9 Service de bactériologie-virologie-hygiène, CHRU Tours, Tours, France
  1. Correspondence to Dr Jean-Baptiste Delaye, Service de Biochimie et Biologie Moléculaire, CHRU Tours, Tours 37044, Centre, France; J.DELAYE{at}


Iron metabolism is tightly linked to infectious and inflammatory signals through hepcidin synthesis. To date, iron homeostasis during SARS-CoV-2 infection has not yet been described. The aim of this study is to characterize the hepcidin and erythroid regulators (growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE)) by measuring concentrations in plasma in context of COVID-19 disease.

We performed a single-center observational study of patients with COVID-19 to evaluate concentrations of main regulatory proteins involved in iron homeostasis, namely: hepcidin, ERFE and GDF-15. SARS-CoV-2 infection (COVID-19+) was defined by a positive RT-PCR. Sixteen patients with COVID-19+ were gender-matched and age-matched to 16 patients with a sepsis unrelated to SARS-CoV-2 (COVID-19) and were compared with non-parametric statistic test.

Clinical and hematological parameters, plasma iron, transferrin, transferrin saturation, ferritin, soluble transferrin receptor and C reactive protein were not statistically different between both groups. Median plasma hepcidin concentrations were higher in the COVID-19+ group (44.1 (IQR 16.55–70.48) vs 14.2 (IQR 5.95–18.98) nmol/L, p=0.003), while median ERFE and GDF-15 concentrations were lower in the COVID-19+ group (0.16 (IQR 0.01–0.73) vs 0.89 (IQR 0.19–3.82) ng/mL, p=0.035; 2003 (IQR 1355–2447) vs 4713 (IQR 2082–7774) pg/mL, p=0015), respectively) compared with the COVID-19 group.

This is the first study reporting lower ERFE and GDF-15 median concentrations in patients with COVID-19+ compared with patients with COVID-19, associated with an increased median concentration of hepcidin in the COVID-19+ group compared with COVID19 group.

  • COVID-19
  • iron
  • inflammation

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • J-BD and HA contributed equally.

  • Contributors J-BD and HA collected and analyzed research data, and wrote the initial draft of the manuscript. MR collected research data and contributed to the writing of the manuscript. EP and HB designed the study and contributed to the writing of the manuscript. NV, LB, OH, JM, CV-D, EG and CR contributed to the writing of the manuscript. EP is responsible for the overall content as the guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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