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)