{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hanson AL"],"funding":["RCUK | MRC | Medical Research Foundation","Medical Research Council","EC | Horizon 2020 Framework Programme","Wellcome Trust","NIGMS NIH HHS"],"pagination":["471-482"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10907301"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(3)"],"pubmed_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."],"journal":["Nature immunology"],"pubmed_title":["Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19."],"pmcid":["PMC10907301"],"funding_grant_id":["T32 GM008719","MC_UU_00008/10","MC_UU_00036/4","MR/L019027/1","200871/Z/16/Z","MC_PC_17230","733100","MR/W018861/1"],"pubmed_authors":["Bradley JR","Hess C","Nathan JA","Hanson AL","Mule MP","Gottgens B","Drakesmith H","Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration","Kotagiri P","Pelly VS","Gleadall N","Lyons PA","Smith KGC","Mescia F","Bergamaschi L","Turner L","Ruffieux H"],"additional_accession":[]},"is_claimable":false,"name":"Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-11T06:13:23.033Z","creation":"2026-06-11T03:13:03.423Z"},"accession":"S-EPMC10907301","cross_references":{"pubmed":["38429458"],"doi":["10.1038/s41590-024-01754-8"]}}