Repository logo

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

Accepted version



Change log


Mulè, Matthew P 
Bergamaschi, Laura 


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.



Humans, Iron, Erythropoiesis, COVID-19, SARS-CoV-2, Research Personnel, Disease Progression

Journal Title

Nat Immunol

Conference Name

Journal ISSN


Volume Title


Nature Research
Wellcome Trust (200871/Z/16/Z)
Medical Research Council (MR/L019027/1)
Evelyn Trust (20/75)
MRC (via University of Birmingham) (1744863)
MRC (via University of Birmingham) (UK CIC UOB160996)
European Commission Horizon 2020 (H2020) Societal Challenges (733100)
Medical Research Council (MR/W018861/1)