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)

Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation

Abstract:

Abstract available online: https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

Source: S. Jothi, G. Claessen, M. Insel, S. Kubba, E. Howden, S.-R. Carmona, F.P. Rischard. Post-acute Sequelae of SARS Co-V2 and Chronic Fatigue/Myalgic Encephalitis Share Similar Pathophysiologic Mechanisms of Exercise Limitation. https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A6470

ME/CFS may be linked to failure in energy supply to the cells

By Elise Kjørstad

Researchers at the University of Bergen and Haukeland University Hospital were part of a research team for a new study that found differences in blood samples between ME/CFS patients and healthy people.

Patients with myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, had different levels of some substances that affect energy metabolism in the cells.

“What we think might be an explanation is that restricted blood flow during activity means the cells are receiving too little oxygen, and this leaves metabolic traces over time,” says Karl Johan Tronstad.

In the new study, the researchers performed an analysis of metabolites and other substances in blood samples from ME/CFS patients. Metabolites are metabolic products that are created when the cells convert different substances in the body.

The researchers analysed blood samples from 83 individuals with ME/CFS and 35 healthy controls.

The researchers measured about 1700 substances in the blood samples they took.

In the ME/CFS patients, they found an altered level of over 300 substances. Many of them involved the conversion of amino acids, which build up proteins, and lipids (fats).

Read the rest of this article HERE.

 

 

Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls

Abstract:

AIMS: To investigate the possibility of a correlation between the percentage of nondiscocytic erythrocytes and muscle fatiguability in subjects with the symptom of chronic tiredness.

METHODS: Sixty nine volunteers suffering from persisting or intermittent tiredness and 72 healthy controls provided 3-drop samples of venous blood for red cell shape analysis before and after inducing fatigue in the trigger finger muscles by repeatedly pulling the trigger of an antique revolver. Elapsed time and the number of pulls were recorded. A work index was calculated from the number of trigger pulls divided by the time in seconds then multiplied by the number of trigger pulls.

RESULTS: Subjects with tiredness had fewer discoid cells (males 62.5% vs 69.2%, p = 0.029; females 65.8% vs 71.8%, p = 0.002) than controls. They also had fewer trigger pulls (males 62.3 vs 84.0, p = 0.003; females 29.5 vs 36.8, p = 0.042) and lower “work indices” (males 75.6 vs 104.7, p = 0.001; females 26.1 vs 39.6, p = 0.001) than controls at the first trigger pulling. After 5 minutes rest the number of trigger pulls for males was fewer than the controls (56.0 vs 64.2) but the difference was not significant, but the female values (24.3 vs 33.2) were significantly different (p = 0.008). Work indices for both sexes were significantly different from controls (males p = 0.020, females p = 0.001).

CONCLUSIONS: The association of increased nondiscocytes and impaired muscle function could indicate a cause and effect relationship. This would be in agreement with the physiological concept of fatigue as a consequence of inadequate oxygen delivery.

 

Source: Simpson LO, Murdoch JC, Herbison GP. Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls. N Z Med J. 1993 Mar 24;106(952):104-7. http://www.ncbi.nlm.nih.gov/pubmed/8474717

 

Chronic tiredness and idiopathic chronic fatigue–a connection?

Abstract:

Evidence is adduced to support the proposal that pathological fatigue is a consequence of impaired capillary blood flow resulting in inadequate oxygen delivery, which is in accordance with physiological concepts of fatigue. Case reports are presented.

Comment in: Chronic fatigue syndrome. [N J Med. 1992]

 

Source: Simpson LO. Chronic tiredness and idiopathic chronic fatigue–a connection? N J Med. 1992 Mar;89(3):211-6. http://www.ncbi.nlm.nih.gov/pubmed/1574202