- Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
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Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Nature Immunology volume 25, pages471–482 (2024)
Aimee L. Hanson, Matthew P. Mulè, Hélène Ruffieux, Federica Mescia, Laura Bergamaschi, Victoria S. Pelly, Lorinda Turner, Prasanti Kotagiri, Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration, Berthold Göttgens, Christoph Hess, Nicholas Gleadall, John R. Bradley, James A. Nathan, Paul A. Lyons, Hal Drakesmith & Kenneth G. C. Smith
Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC.
A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity.
A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes.
Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.
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Diseases associated with
| Low iron (menstruating) | High iron (males) |
| Anemia | Anemia of chronic disease |
| Fibromyalgia | Premature aging |
| Inflammatory bowel disease | Atherosclerosis |
| Hypothyroidism | Anorexia |
| Depression / anxiety | Grave's disease |
| Attention deficit hyperactivity disorder | Heart arrhythmia |
| Parkinson's disease | Cancer |
| Neurodegenerative conditions | Sideroblastic anemia |
| Celiac disease | Nonalcoholic fatty liver disease (NAFLD). Excess dietary fructose is a primary initiator of NAFLD, but high iron is another culprit that triggers disease progression |
| Restless leg syndrome | Liver damage and liver disease |
| Hair loss | Still's disease |
| Muscle weakness, decline in motor skills | Hemochromatosis |
| Mental changes and memory loss | Hemophagocytic syndrome |