Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19

Abstract:

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.

Source: Hanson AL, Mulè MP, Ruffieux H, Mescia F, Bergamaschi L, Pelly VS, Turner L, Kotagiri P; Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration; Göttgens B, Hess C, Gleadall N, Bradley JR, Nathan JA, Lyons PA, Drakesmith H, Smith KGC. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19. Nat Immunol. 2024 Mar;25(3):471-482. doi: 10.1038/s41590-024-01754-8. Epub 2024 Mar 1. PMID: 38429458; PMCID: PMC10907301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907301/ (Full text)

Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities

Abstract:

Chronic fatigue syndrome is defined by the Atlanta Centers for Disease Control (Atlanta, GA, USA) as debilitating fatigue lasting for longer than 6 months. Symptoms include disturbances of cognition. Certain factors have in the past been shown to influence cognition, including metals such as aluminum, iron, and zinc; and steroids such as dehydroepiandrosterone.

In the present study, concentrations of these factors were determined in the serum and plasma of patients and their age- and gender-matched healthy controls (10 women and 5 men in each group). In addition, copper, dehydroepiandrosterone sulphate, cortisol, cholesterol, hemoglobin, ferritin and transferrin concentrations, as well as transferrin genetic subtypes were determined in both groups.

The results indicate that patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated. Total cholesterol was significantly increased, and significantly negatively correlated with dehydroepiandrosterone sulphate. There were no differences in zinc, copper, cortisol, hemoglobin, transferrin and ferritin concentrations, or in transferrin genetic subtypes.

 

Source: van Rensburg SJ, Potocnik FC, Kiss T, Hugo F, van Zijl P, Mansvelt E, Carstens ME, Theodorou P, Hurly PR, Emsley RA, Taljaard JJ. Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities. Brain Res Bull. 2001 May 15;55(2):319-25. http://www.ncbi.nlm.nih.gov/pubmed/11470334