Hemoglobin and Iron Dynamics in COVID-19 Pathogenesis

The interplay between haemoglobin integrity and iron homeostasis is emerging as a critical determinant of disease severity in COVID-19. SARS-CoV-2 infection triggers a systemic inflammatory response that alters iron trafficking and storage, leading to elevated ferritin levels, disrupted hepcidin regulation and reduced circulating iron. These changes contribute to anaemia of inflammation, impaired oxygen delivery and tissue hypoxia. Concurrently, viral interactions with erythrocyte precursors and spike-protein-mediated ferroportin blockade may exacerbate haemoglobin denaturation and intracellular iron overload. The resulting hyperferritinaemia and free heme release potentiate oxidative stress, endothelial injury and coagulopathy. Moreover, iron-dependent lipid peroxidation, known as ferroptosis, has been implicated in multi-organ dysfunction. Together, these mechanisms create a vicious cycle of inflammation, iron dysregulation and impaired erythropoiesis that underpins adverse clinical outcomes. Understanding these pathways offers avenues for therapeutic intervention, including modulation of hepcidin, iron chelation and targeted inhibition of ferroptosis, with the aim of restoring vascular oxygenation and reducing organ injury.

Research from Nature Portfolio

In a large multicentre cohort study, the presence of anaemia at hospital admission was identified as an independent predictor of severe COVID-19 and in-hospital mortality. Patients with lower haemoglobin exhibited higher baseline levels of inflammatory markers such as C-reactive protein, procalcitonin and interleukin-6, alongside elevated serum ferritin. After adjusting for age, comorbidities and other confounders, anaemia remained significantly associated with a two-to threefold increase in the risk of mechanical ventilation and death. Propensity-score analyses confirmed that impaired erythropoiesis and iron sequestration represent key drivers of poor prognosis, underscoring the prognostic value of simple haematological parameters in risk stratification.

Hemoglobin and Iron Dynamics in COVID-19 Pathogenesis publication trend

The graph below shows the total number of articles in hemoglobin and iron dynamics in covid-19 pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Haemoglobin: Oxygen-transport metalloprotein in erythrocytes composed of globin chains and iron-containing heme groups.

Ferritin: Intracellular protein complex that stores iron and reflects total body iron reserves as well as acute inflammation.

Hepcidin: Liver-derived peptide hormone that regulates systemic iron by binding to ferroportin and reducing iron export.

Ferroptosis: Regulated form of cell death driven by iron-dependent lipid peroxidation and loss of membrane integrity.

Anaemia of inflammation: Reduction in haemoglobin concentration caused by cytokine-mediated iron sequestration and impaired erythropoiesis.

References

1. Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19. Pharmaceutics (2023).
2. Toward improved human health: Ferroptosis‐related “Hyperfoods” as the nutritional supplement in COVID‐19. eFood (2024).
3. Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study. Scientific Reports (2023).
4. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clinics and Practice (2020).