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Do low iron levels explain long COVID symptoms?

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Researchers have identified a potential new culprit in long COVID: low iron levels. Image credit: Natalia Lebedinskaia/Getty Images.
  • The peak of the COVID-19 pandemic may be in the past but, for many people, its effects persist in the form of long COVID.
  • With symptoms ranging from fatigue to digestive problems and brain fog, long COVID can have a profound impact on a person’s daily functioning.
  • The cause is still unclear, but a new study has found a strong link between a disruption in iron levels during acute COVID-19 and long COVID.
  • The researchers suggest this might indicate new avenues for preventing and treating long COVID.

As of mid-February this year, the World Health Organization (WHO) had recorded nearly 775 million cases of COVID-19 worldwide.

Infection with SARS-CoV-2 Trusted Source Centers for Disease Control and Prevention (CDC) Governmental authority Go to source , the virus that causes COVID-19, often results only in a mild illness, but for some it can lead to hospitalization and even death. 

However severe the initial infection, for some people COVID-19 leaves behind an unwelcome legacy — long COVID Trusted Source Centers for Disease Control and Prevention (CDC) Governmental authority Go to source . Research Trusted Source International Journal of Obesity Peer reviewed journal Go to source suggests that up to 10% of people who become ill with SARS-CoV-2 may go on to develop long COVID, and as many as 50% to 70% of those hospitalized with COVID-19 experience ongoing symptoms.

These long COVID symptoms may include:

  • tiredness or fatigue that interferes with daily life
  • a worsening of symptoms after physical or mental effort (post-exertional malaise)
  • breathlessness
  • chest pain and heart palpitations
  • brain fog
  • sleep problems
  • stomach pain and diarrhea.

The cause of long COVID is currently unknown, but new research, published in Nature Immunology Trusted Source International Journal of Obesity Peer reviewed journal Go to source , has found a link between disruption in iron levels during the initial illness and long COVID symptoms. 

Arturo Casadevall, the chair of Molecular Microbiology & Immunology and a professor at the Johns Hopkins Bloomberg School of Public Health in Maryland who was not involved in this research, told Medical News Today:

“The paper reports altered iron metabolism in association with post-COVID sequelae (PASC) or long COVID, including low serum iron. As the authors note, the results are not surprising since long COVID is an inflammatory condition and inflammation is often associated with reduced iron levels.”

Why study iron levels after COVID-19?

Many of the symptoms seen in long COVID are similar to those caused by low iron levels, or iron-deficiency anemia, so the researchers investigated the effect of SARS-CoV-2 on iron metabolism.

The researchers assessed 214 people who had been come down with the virus, leading to COVID-19 of varying severity, for 1 year after the initial onset of symptoms.

The researchers divided the participants into five groups depending on the severity of their COVID-19 symptoms:

  1. asymptomatic
  2. mildly symptomatic
  3. moderate without supplemental oxygen requirement
  4. moderate with supplemental oxygen requirement
  5. severe with assisted ventilation

The participants ranged in age from 17 to 89 years with groups 3 through 5 being mostly older. All those in the groups 3 to 5 were hospitalized during their illness. Those in groups 1 and 2 were not. 

The researchers took matched blood, plasma and serum samples at various time points up to day 352 after symptom onset — or the first positive swab for the asymptomatic group. They matched these with samples from people who had never had COVID-19.

How COVID-19 disrupts iron metabolism

The researchers said they found several immune cell abnormalities during and after COVID-19, with this immunological disruption persisting longest in those who had experienced the most severe symptoms.

In those who were hospitalized, the researchers found that high levels of inflammation during acute illness were accompanied by disrupted iron metabolism. This, together with raised levels of the iron-regulating hormone hepcidin Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source , led to a decrease in serum iron levels. 

These participants also had increased concentrations of the iron storage protein ferritin, which remained high up to 180 days after infection, indicating ongoing inflammation and iron retention by cells.

Conversely, the participants’ serum iron levels were low during the acute infection and in the most severely affected group, remained low up to day 270 after infection.

Altered availability of iron affects the levels of hemoglobin in red blood cells (erythrocytes) that transport oxygen around the body. In the more severely affected groups, hemoglobin remained low up to 90 days post-infection. 

Low serum iron, high serum ferritin and high serum hepcidin are characteristic of inflammatory anemia Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source , which is common with many illnesses, and leads to fatigue, weakness, reduced cardiovascular performance and exercise tolerance, and impaired learning and memory capacity.

Participants in groups 1 and 2 showed little systemic inflammation and no disruption of iron levels.

In a press release, Dr. Aimee Hanson, a senior research associate now at the University of Bristol who worked on the study while at the University of Cambridge, said: 

“Iron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months later.”

“Although we saw evidence that the body was trying to rectify low iron availability and the resulting anaemia by producing more red blood cells, it was not doing a particularly good job of it in the face of ongoing inflammation,” she added.

What might this mean for long COVID treatments?

Iron dysregulation is a natural response to infection, as the body responds by removing iron from the bloodstream to deprive pathogens Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source of that essential mineral.

However, if the immune response and resulting inflammation persist, then red blood cells are deprived of iron, leading to the symptoms seen in anemia and in many people with long COVID.

However, Hanson pointed out that it was not a deficiency of iron, but how iron was distributed in the body that was likely to be causing the problem.

“It isn’t necessarily the case that individuals don’t have enough iron in their body, it’s just that it’s trapped in the wrong place,” she said. “What we need is a way to remobilize the iron and pull it back into the bloodstream, where it becomes more useful to the red blood cells.”

Casadevall agreed, noting that:

“The findings raise the possibility that some of the symptoms of long COVID are the result of altered iron metabolism. Patients with long COVID should not interpret the results of this study as suggesting that iron supplementation is the answer to their symptoms, since too much iron can be toxic. Instead, they should consult their physicians as to whether iron supplementation is warranted.”

“The importance of this paper is that it suggests a new angle for investigation in long COVID involving the role of iron. Knowing how to use these findings in clinical practice will require additional clinical studies,” he added.

This article originally appeared on Medical News Today.

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