Low iron levels could be key trigger of long COVID

By James Gamble via SWNS

Low levels of iron could be a key trigger for those suffering with long COVID-19, a new study has found.

Researchers found patients exhibiting symptoms of COVID-19 months after their initial infection often had low levels of iron in their blood.

However, iron supplements may not prove a cure as iron 'dysregulation' doesn't necessarily mean people have insufficient levels of iron, just that it's 'trapped in the wrong place'.

But the study, from scientists led by the University of Cambridge, could still help those suffering with symptoms of long COVID.

Although estimates are highly contested, as many as three in ten people infected with SARS-CoV-2 could go on to develop long COVID, which includes symptoms of fatigue, shortness of breath, muscle aches and problems with memory and concentration, often referred to as "brain fog."

According to the Office for National Statistics, nearly two million people in the UK had self-reported symptoms of long COVID-19 as of March 2023.

Shortly after the beginning of the pandemic, researchers at the University of Cambridge began recruiting participants who had tested positive for the virus to the COVID-19 National Institute for Health and Care Research (NIHR) BioResource cohort.

These included some asymptomatic healthcare staff identified via routine screening and patients admitted to Cambridge University Hospitals NHS Foundation Trust - some of whom were admitted to its intensive care unit.

Over the space of a year, participants provided blood samples to allow researchers to monitor changes in the blood following their COVID-19 infections.

As it became clear that a significant number of patients would go on to have symptoms that persisted - or long COVID - the researchers were able to track these samples to see whether any changes in the blood correlated with their later condition.

The study, published in the journal Nature Immunology, analyses samples from a total of 214 individuals.

Nearly half (45 percent) of those questioned about their recovery reported symptoms of long COVID between three and ten months later.

Professor Ken Smith, the Director of CITIID at the time of the study who is now based in Melbourne, Australia, explained: "Having recruited a group of people with SARS-CoV-2 early in the pandemic, analysis of several blood samples and clinical information collected over a 12 month period after infection has proved invaluable in giving us important and unexpected insights into why, for some unlucky individuals, initial SARS-CoV-2 infection is followed by months of persistent symptoms.”

The research team discovered that ongoing inflammation - a natural part of the immune response to infection - and low iron levels in the blood, contributing to anemia and disrupting healthy red blood cell production, could be seen as early as two weeks after COVID infections in those reporting long COVID months later.

Early iron dysregulation was detected in those with long COVID-19 independent of age, sex, or initial COVID-19 severity, suggesting a possible impact on recovery even in those who were at low risk for severe COVID-19 or who did not require hospitalization or oxygen therapy when initially infected.

Dr. Aimee Hanson, now at the University of Bristol, 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 anemia by producing more red blood cells, it was not doing a particularly good job of it in the face of ongoing inflammation.”

Although iron dysregulation was more profound during and following severe COVID-19, the researchers found that those who went on to develop long COVID-19 after a milder course of COVID-19 interestingly showed similar patterns in the blood.

The most pronounced association with long COVID was how quickly inflammation, iron levels and regulation returned to normal following SARS-CoV-2 infection - though symptoms tended to continue long after iron levels had recovered.

Professor Hal Drakesmith, a co-author of the study from the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, said iron dysregulation is a common consequence of inflammation and is a natural response to infection.

“When the body has an infection, it responds by removing iron from the bloodstream," he explained.

"This protects us from potentially lethal bacteria that capture the iron in the bloodstream and grow rapidly.

"It’s an evolutionary response that redistributes iron in the body, and the blood plasma becomes an iron desert.

“However, if this goes on for a long time, there is less iron for red blood cells, so oxygen is transported less efficiently affecting metabolism and energy production, and for white blood cells, which need iron to work properly.

"The protective mechanism ends up becoming a problem.”

The researchers suggested their findings may help to explain why fatigue and exercise intolerance are common in long COVID, as well as in several other post-viral syndromes with lasting symptoms.

They add that their study points to potential ways of preventing or reducing the impact of long COVID-19 by rectifying iron dysregulation during early COVID-19 infections to prevent adverse long-term health outcomes.

One approach could be to control the extreme inflammation as early as possible before it impacts iron regulation.

However, the obvious approach of iron supplementation may not be straightforward.

“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,” Dr. Hanson 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.”

This latest study also supports ‘accidental’ findings from other studies, including the IRONMAN study, which looked at whether iron supplements benefited patients with heart failure.

The study was disrupted due to the pandemic, but preliminary findings suggest that trial participants taking the supplements were less likely to develop severe adverse effects from COVID-19.

Similar effects have been observed among people living with the blood disorder beta-thalassemia, which can cause individuals to produce too much iron in their blood.