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Summary of COVID-19 and Iron Zoomposium

An online zoomposium presenting and discussing data on iron homeostasis in COVID-19 took place of September 8 hosted by the European Iron Club. It was attended by around 230 people from around the world, the majority in Europe. Attendees were physicians and scientists from academia and industry as well as representatives from patient groups and funding organisations. After an introduction on basics of iron homeostasis and the trajectory of COVID-19 disease, there were eight further data presentations. These described aspects of iron-related parameters, haematology and disease severity in cohorts of COVID-19 patients from Germany, Austria, Italy and the UK. The presenters were: Martina Muckenthaler and Uta Merle (Heidelberg); Guenter Weiss and Heinz Zoller (Innsbruck); Elena Corradini (Modena) and Fabiana Busti (Verona); and Hal Drakesmith and Akshay Shah (Oxford).

There were variations in the types of patients described, for example out-patient, in-patient, ICU; data was presented derived from single-timepoint or longitudinal sample sets, and there were differences in the parameters measured, the degree of severity of illness, the time window within the pandemic that the data was collected, and the treatments the patients were receiving. These differences meant that in some respects, datasets could not be compared between groups. However, despite this heterogeneity of patients and the unavoidable differences in reporting, there was enough overlap to produce some clear messages.

Perhaps the key finding was that hypoferraemia is particularly pronounced (<5umol/L, TSAT lower than 5% in several studies) in severe COVID-19 disease, and may be more marked in COVID-19 patients in intensive care than in patients in intensive care for other reasons, including sepsis. Furthermore, low serum iron and/or TSAT appear to have predictive value in terms of oxygen requirements and mortality. Hyperferritinaemia is commonly observed, but does not usually reach the extremely high concentrations seen in patients with macrophage activation syndrome, and is less useful to guide patient management; however, the ferritin / transferrin ratio may have more prognostic value. The cause of very low serum iron is not entirely clear; increased hepcidin occurs in COVID-19 patients but correlative analyses indicated other as yet unknown factors may also contribute to hypoferraemia during the course of disease.

The presentations highlighted several further key unknowns:

  1. What is the role of the EPO-Erfe (and/or other erythroid regulators)-hepcidin axis in hypoxaemic patients and response to ventilation?
  2. What are the downstream effects of prolonged hypoferraemia, along with inflammation, on immunity, cardiac function, and other aspects of COVID-19 pathophysiology?
  3. Would treatments that directly counteract hypoferraemia be useful in any way?
  4. Do current steroidal or biological anti-inflammatories provide benefit at least in part via effects on iron?
  5. What effects do underlying iron deficiency or iron overload (haemochromatosis or thalassaemia) have on progression of infection?
  6. Do genetic variants that are known to influence the progression of infection (eg blood group) act in part via effects on iron?

Finally, as infections continue to rise worldwide, and increase again across Europe as the seasons change, awareness of the above points should inform future data collection and reporting; specifically, serum iron, TSAT and if possible hepcidin, Epo and Erfe should be measured in longitudinal samples along with standard clinical metadata. Where possible, iron related parameters in the lung should also be measured, and interactions of iron and immune status (antibody, inflammatory mediators) should be investigated. The prevalence and severity of anaemia should be assessed both in patients in the acute phases of infection but also during recovery; does failure to resolve anaemia play any role in so-called “long COVID?”

In the concluding session there were presentations and discussions on the issue of information sharing. There was a general feeling that to help gather data, increase our “n”, and improve compatibility of reporting, we should as a community keep in contact and explore data sharing and distribution platforms and collaborative work, and grants.

If any member of BioIron wishes to discuss any of the issues raised above, please feel free to contact Hal Drakesmith (alexander.drakesmith@imm.ox.ac.uk) or Heinz Zoller (heinz.zoller@i-med.ac.at).

Hal Drakesmith
President, European Iron Club

posted: October 2, 2020