Iron dysregulation linked to long COVID development
According to new research, SARS-CoV-2 infection-related issues with blood iron levels and the body’s capacity to control this vital nutrient may be a major cause of protracted COVID-19. The finding may help explain why symptoms resembling those of long-term COVID are also frequently observed in a variety of post-viral disorders and chronic inflammation, in addition to suggesting potential preventative or therapeutic measures.
Although estimates vary greatly, up to three out of ten individuals infected with SARS-CoV-2 may develop long-term COVID-19, which manifests as memory and concentration issues (also known as “brain fog”), exhaustion, shortness of breath, and muscle aches. As of March 2023, the Office of National Statistics estimates that 1 in 9 people in the UK alone were suffering from self-reported long COVID-19.
Researchers at the University of Cambridge started adding individuals who had tested positive for the virus to the COVID-19 cohort of the National Institute for Health and Care Research (NIHR) BioResource shortly after the COVID-19 pandemic began. These ranged from patients admitted to the Cambridge University Hospitals NHS Foundation Trust, some of whom were admitted to the intensive care unit, to asymptomatic medical personnel found through routine screening.
Participants gave blood samples for a year, which allowed researchers to track changes in the blood after infection. As it became evident that many patients would experience long-lasting COVID symptoms, researchers were able to follow up on these samples to determine whether any blood changes were associated with the patients’ subsequent health. Researchers from the University of Cambridge’s Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), along with colleagues from Oxford, examined blood samples from 214 people for their findings, which were published in Nature Immunology. When asked about their recovery, about 45% of respondents said they experienced long-term COVID-19 symptoms three to ten months later.
Having recruited a group of people with SARS-CoV-2 early in the pandemic, analysis of several blood samples and clinical information collected over 12 months after infection has proven invaluable in giving us important and unexpected insights into why, for some unfortunate individuals, initial SARS-CoV-2 infection is followed by months of persistent symptoms, said Professor Ken Smith, who was Director of CITIID at the time of the study and will start a new role as Director of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, in April.
As early as two weeks after COVID-19, the team found that in those who reported long COVID many months later, persistent inflammation—a normal component of the immune response to infection—and low blood iron levels, which lead to anemia and interfere with the production of healthy red blood cells, could be observed. Regardless of age, sex, or the initial severity of COVID-19, early iron dysregulation was found in the long COVID group. This suggests that recovery may be impacted even in individuals who were not at high risk for severe COVID-19 or who did not need hospitalization or oxygen therapy when ill. It took a very long time to recover from the early disruption of iron levels and the body’s ability to regulate iron during SARS-CoV-2 infection, especially for those who reported long COVID months later.
In the face of persistent inflammation, we observed evidence that the body was not doing a very good job of producing more red blood cells in an attempt to address low iron availability and the ensuing anemia. It’s interesting to note that individuals who developed long COVID after a milder course of acute COVID-19 displayed comparable blood patterns, even though iron dysregulation was more severe during and after severe COVID-19. Although symptoms tended to persist long after iron levels had recovered, the most notable correlation with long COVID was the speed at which inflammation, iron levels, and regulation returned to normal after SARS-CoV-2 infection. stated that iron dysregulation is a normal reaction to infection and a frequent result of inflammation.
The body eliminates iron from the bloodstream in response to an infection. This shields us from potentially fatal bacteria that quickly grow and absorb iron from the blood. The body redistributes iron as a result of this evolutionary response, turning the blood plasma into an iron desert. On the other hand, if this continues for a long period, there will be less iron for white blood cells, which require iron to function properly, and red blood cells, which means oxygen is transported less effectively, impacting metabolism and energy production. In the end, the protective mechanism becomes problematic.
The results could help explain why long-term COVID-19 and some other post-viral syndromes with persistent symptoms frequently exhibit symptoms like fatigue and exercise intolerance. By correcting iron dysregulation in early COVID-19, the study suggests possible strategies to prevent or lessen the effects of long COVID-19 to avoid negative long-term health outcomes, according to the researchers.
One strategy could be to manage the severe inflammation as soon as possible before it affects the regulation of iron. Iron supplementation could be another strategy, but as Dr. Hanson noted, this might not be simple. People may not actually have insufficient iron in their bodies; rather, it may simply be stored in the wrong location. The iron must be remobilized and drawn back into the bloodstream so that the red blood cells can use it more effectively.
The study also confirms “accidental” findings from other research, such as the IRONMAN study, which examined the potential benefits of iron supplements for heart failure patients. The study was interrupted by the COVID-19 pandemic, but initial results indicate that trial participants had a lower risk of experiencing serious side effects from COVID-19. People who have beta-thalassemia, a blood disorder that can lead to excessive iron production in the blood, have seen similar effects.