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2024-04-01| COVID-19

Iron Dysregulation Linked to Long COVID Outcomes

by Bernice Lottering
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Recent research indicates a significant connection between iron levels, inflammation, and the emergence of long COVID following SARS-CoV-2 infection. It has been observed that defects in iron homeostasis, dysregulated erythropoiesis, and immune dysfunction due to COVID-19 may contribute to inefficient oxygen transport, inflammatory imbalances, and persisting symptomatology. These findings suggest that early intervention in iron regulation could hold therapeutic promise in managing long-term symptoms associated with COVID-19.

Long COVID: Research Initiatives and Clinical Observations

New research has found that issues with iron levels in the blood and the body’s ability to regulate this vital nutrient due to SARS-CoV-2 infection could be a significant factor in triggering long COVID. 

Post-acute sequelae of COVID-19, commonly referred to as long COVID, presents a complex clinical picture with a range of persistent symptoms lasting ≥3 months after infection. Up to 30% of individuals infected with SARS-CoV-2 may develop long COVID, experiencing symptoms like breathing difficulties, fatigue, and cognitive issues. Factors contributing to long COVID include features of acute COVID-19, immune changes persisting for months, and various predictors such as female sex and increased viral load. In the UK alone, an estimated 1.9 million people reported experiencing long COVID as of March 2023, according to the Office of National Statistics. As the understanding regarding the nature and impact of long COVID grows, it is expected that this number will continue to rise.

During the early stages of the COVID-19 pandemic, University of Cambridge researchers recruited individuals who tested positive for the virus, including asymptomatic healthcare workers and hospitalized patients, into the COVID-19 cohort of the National Institute for Health and Care Research (NIHR) BioResource. Over the following year, participants provided blood samples for monitoring post-infection, allowing investigators to analyze biological changes over time and investigate correlations with persistent symptoms, known as long COVID.

A Lengthy Study of Long COVID

The investigation, published in Nature Immunology, was conducted by researchers at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, in collaboration with colleagues at Oxford. It revealed that issues with iron levels in the blood and the body’s ability to regulate this crucial nutrient following SARS-CoV-2 infection may serve as a significant catalyst for long COVID. In blood samples from 214 individuals, approximately 45% of participants reported symptoms of long COVID between 3 and 10 months after their initial infection. Analyzing blood samples and clinical information collected from individuals with early SARS-CoV-2 infection over a 12-month period has provided valuable insights into why some people experience persistent symptoms after the initial infection.

Understanding Mechanisms and Treatment Implications

Early disruptions in iron regulation were observed in individuals who later experienced long COVID symptoms, with ongoing inflammation and low iron levels noted as early as two weeks post-COVID-19 infection. Dr. Aimee Hanson from the University of Cambridge highlighted the prolonged recovery of iron levels, indicating a challenge in rectifying low iron availability despite increased red blood cell production.

Interestingly, while severe cases of COVID-19 were associated with more significant disruptions in iron levels and regulation, individuals with milder cases also experienced similar blood patterns. The most notable factor linked to long COVID was how rapidly inflammation, iron levels, and regulation returned to normal after SARS-CoV-2 infection, even though symptoms persisted long after these iron levels had returned to normal.

Professor Hal Drakesmith, a co-author from the University of Oxford, emphasized that iron redistribution is a standard physiological response to inflammation and serves as a natural reaction to infection, aimed at protecting against bacterial growth. However, prolonged iron redistribution is dysfunctional and can lead to decreased oxygen transport efficiency, which negatively affects the metabolism and energy production, whilst also impairing white blood cell function. This iron dysregulation is what exacerbates symptoms associated with long COVID and other post-viral syndromes. 

The study suggests addressing iron dysregulation early in COVID-19 to mitigate the impact of long COVID. Strategies may include promptly controlling inflammation and exploring iron supplementation options, although Dr. Hanson noted the complexity involved in effectively mobilizing iron to support red blood cell function.

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