tetano
Editor, Senior Moderator
Nat Immunol
. 2024 Mar;25(3):471-482.
doi: 10.1038/s41590-024-01754-8. Epub 2024 Mar 1. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Aimee L Hanson[SUP] 1 2 [/SUP], Matthew P Mulè[SUP] 1 2 3 [/SUP], Hélène Ruffieux[SUP] 4 [/SUP], Federica Mescia[SUP] 1 2 [/SUP], Laura Bergamaschi[SUP] 1 2 [/SUP], Victoria S Pelly[SUP] 1 2 [/SUP], Lorinda Turner[SUP] 1 2 [/SUP], Prasanti Kotagiri[SUP] 1 2 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration; Berthold Göttgens[SUP] 5 [/SUP], Christoph Hess[SUP] 1 2 6 7 [/SUP], Nicholas Gleadall[SUP] 8 9 [/SUP], John R Bradley[SUP] 2 10 11 [/SUP], James A Nathan[SUP] 1 2 [/SUP], Paul A Lyons[SUP] 1 2 [/SUP], Hal Drakesmith[SUP] 12 [/SUP], Kenneth G C Smith[SUP] 13 14 15 16 [/SUP]
Affiliations
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.
. 2024 Mar;25(3):471-482.
doi: 10.1038/s41590-024-01754-8. Epub 2024 Mar 1. Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
Aimee L Hanson[SUP] 1 2 [/SUP], Matthew P Mulè[SUP] 1 2 3 [/SUP], Hélène Ruffieux[SUP] 4 [/SUP], Federica Mescia[SUP] 1 2 [/SUP], Laura Bergamaschi[SUP] 1 2 [/SUP], Victoria S Pelly[SUP] 1 2 [/SUP], Lorinda Turner[SUP] 1 2 [/SUP], Prasanti Kotagiri[SUP] 1 2 [/SUP]; Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration; Berthold Göttgens[SUP] 5 [/SUP], Christoph Hess[SUP] 1 2 6 7 [/SUP], Nicholas Gleadall[SUP] 8 9 [/SUP], John R Bradley[SUP] 2 10 11 [/SUP], James A Nathan[SUP] 1 2 [/SUP], Paul A Lyons[SUP] 1 2 [/SUP], Hal Drakesmith[SUP] 12 [/SUP], Kenneth G C Smith[SUP] 13 14 15 16 [/SUP]
Affiliations
- PMID: 38429458
- PMCID: PMC10907301
- DOI: 10.1038/s41590-024-01754-8
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.