Woman lying down suffering from symptoms of long covid after COVID-19
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Research led by the University of Cambridge shows that low iron levels and disrupted iron regulation in the body due to the viral infection may be contributing to long COVID symptoms.

Although reports on exact numbers differ, it is thought that up to 30% of all people infected with SARS-CoV-2 have symptoms that last for three months or more or go on to develop new symptoms weeks after initial infection with the virus. This syndrome has been colloquially named “long COVID” and is now causing significant disability among those affected around the world.

Not long after the COVID-19 pandemic began, a group of researchers in Cambridge recruited people infected with the SARS-CoV-2 virus, ranging from asymptomatic to severe cases, to take part in a study to assess symptoms and long-term outcomes of infection. Patients in the study had their blood tested regularly so when it became clear that some would go on to develop long COVID it was a good opportunity to analyze potential blood changes that could lead to the condition.

The current study, published in the journal Nature Immunology, assessed changes in the blood of 214 individuals with varying levels of SARS-CoV-2 infection over a 12 month period. Of this group, 102 were asked to fill out questionnaires at three to five and nine to ten months after their initial infection and 65% who filled out both questionnaires reported symptoms of long COVID.

The research team found that people with long COVID had signs of extended inflammation in their blood, as well as low iron levels, signs of altered iron regulation after two weeks of infection. This continued over time, with additional signs of poor iron distribution around the body.

“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,” said first author Aimee Hanson, who worked on the study while at the University of Cambridge, and is now at the University of Bristol, in a press statement.

“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.”

Notably, although symptoms of long COVID tend to be worse if people have experienced a serious initial infection, low iron levels and disrupted regulation were also seen in people with long COVID who had milder initial infections.

The body tends to reduce levels of iron in the blood in response to infections, but this can be problematic if it continues long term. “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,” explained co-author Hal Drakesmith, a professor at the MRC Weatherall Institute of Molecular Medicine at the University of Oxford.

“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 say the results could point the way to new treatment options for long COVID and other post viral syndromes but caution it may not be as simple as just giving people iron supplements.

“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,” said Hanson. “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.”

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