New research has revealed that problems with iron levels in the blood and the body’s ability to regulate this vital nutrient could play a major role in the development of long COVID. This discovery opens up potential pathways for treatment and offers insights into why similar symptoms are found in other post-viral conditions.
Long COVID, which affects a significant number of those who recover from COVID-19, is characterized by persistent symptoms such as fatigue, muscle aches, shortness of breath, and “brain fog.” Current estimates suggest that up to 30% of people infected with SARS-CoV-2 may experience long-term symptoms, with around 1.9 million people in the UK reporting long COVID as of March 2023.
The study, led by researchers at the University of Cambridge, started in the early days of the pandemic. They tracked blood samples from people who tested positive for COVID-19, ranging from asymptomatic healthcare workers to severely ill patients. Over a year, these samples allowed the team to monitor changes in blood composition post-infection and explore potential links to long COVID symptoms that developed months later.
Published in Nature Immunology, the study analyzed blood samples from 214 participants, with 45% reporting long COVID symptoms between three and ten months post-infection. Researchers identified that ongoing inflammation and low iron levels in the blood, leading to anemia and disrupted red blood cell production, were apparent as early as two weeks after infection in individuals who would later report long COVID.
The team also found that these changes occurred independently of age, sex, or the severity of the initial COVID-19 infection, suggesting that even those with mild cases could face challenges in recovery. Dr. Aimee Hanson, one of the study’s authors, explained that iron levels were disrupted early during SARS-CoV-2 infection and took a long time to recover in those who went on to develop long COVID.
“We observed that although the body was trying to correct low iron levels by producing more red blood cells, it struggled due to ongoing inflammation,” said Dr. Hanson, now at the University of Bristol.
The study also noted that iron dysregulation was especially pronounced in severe COVID-19 cases, but individuals with mild infections who later developed long COVID showed similar blood patterns. The most significant factor was how quickly inflammation, iron levels, and regulation returned to normal after infection, although long COVID symptoms often persisted even after iron levels had recovered.
Iron dysregulation is a natural immune response to infection. When the body faces an infection, it removes iron from the bloodstream to prevent bacteria from using it to grow. However, if this process continues for too long, it can reduce the amount of iron available for red blood cells, impairing oxygen transport and metabolism.
These findings may explain why common long COVID symptoms such as fatigue and exercise intolerance are also prevalent in other post-viral syndromes. The research suggests potential strategies for preventing or minimizing long COVID, such as addressing iron dysregulation early during COVID-19 recovery.
Dr. Hanson noted that while iron supplementation could help, the real challenge is not a lack of iron but its misplacement in the body. “What we need is a way to mobilize the trapped iron and bring it back into the bloodstream, where it can be used by red blood cells,” she said.
The study’s findings are supported by other research, including the IRONMAN study, which looked at iron supplements for heart failure patients. Early results from this study showed that iron supplementation could reduce the severity of COVID-19 symptoms. Similar findings were observed in individuals with beta-thalassemia, a blood disorder that leads to excess iron in the blood.
This research, funded by Wellcome, the Medical Research Council, NIHR, and the EU Horizon 2020 Programme, offers a promising avenue for tackling long COVID and other conditions involving prolonged inflammation and iron imbalance.
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