Attacks on our immune system cause Long Covid

There is increasing evidence that Long Covid may be caused by the immune system attacking the body. The results of four studies add to the idea that autoimmunity, in which the immune system damages healthy tissue, is a factor in at least some cases, especially if pain is a primary symptom.

This may one day lead to treatments that are sorely lacking for long-standing disease; There are no approved treatments in the UK or US. “We need to get antibodies from patients and see if the symptoms go away,” says Niels Eijkelkamp at Utrecht University in the Netherlands.

While most people infected with SARS-CoV-2 recover within a few days, some develop symptoms that can last for months or years. There are many variations, but the most common ones include fatigue, pain, brain fog, and post-exertion malaise, in which even light activity causes exhaustion.

Researchers have identified several mechanisms that may contribute to long-term COVID, including persistence of SARS-CoV-2 in the body and dysfunction of the gut microbiome. In any one person suffering from long COVID, one or more of these mechanisms may be at work, which may explain both the range of symptoms and the difficulty of finding a widely applicable treatment.

One much-discussed possible mechanism is autoimmunity, in which the immune system – that is, antibodies – attack the body. Antibodies are supposed to bind to molecules of pathogens, which can then be targeted for destruction, but sometimes the immune system makes a mistake and creates “autoantibodies” that attach to the body’s cells.

An early indication that autoantibodies contribute to long-lasting Covid came in 2023, when researchers Filtered the blood of people suffering from Long Covid Using a technique called apheresis. It was associated with lower levels of autoantibodies and improved symptoms, but so many substances were filtered out that it was not possible to determine which one was responsible.

Now, Ejkelkamp and colleagues have presented evidence that autoantibodies may actually cause some long-lasting COVID symptoms. In early 2022, they studied 34 people with the condition, as well as 15 control subjects who were infected with SARS-CoV-2 but did not develop long COVID. The team focused on a very prevalent set of antibodies called immunoglobulin G (IgG) within the participants’ blood, which they injected into mice.

When these antibodies came from people with long-term Covid, the mice became more sensitive to touch, even gentle ones, and pain. They pulled their paws off the hot surface more quickly than the controls. Eyzkelkamp says the increased pain sensitivity matches what’s seen in some people with long COVID.

When the team repeated the experiment in 2024 using IgG from 19 participants who were still suffering from long-term Covid, they saw the same effect. Says, “These autoantibodies continue to exist in the patients’ body.” charles nikasse at the University of Namur in Belgium, which was involved in one of the four studies.

This echoes the results of three other papers, none of which have yet been peer-reviewed.

Firstly, under the leadership of Akiko Iwasaki at Yale University and released in July 2024, found similarly People with long-term Covid had higher levels of autoantibodies in their bloodAnd people with neurological symptoms had autoantibodies that targeted proteins in the nervous system. Transferring these into mice made them more sensitive to touch and pain, and they began to struggle with balance and coordination, just as people suffering from long-term Covid sometimes experience dizziness.

The remaining two studies were released in November 2025. The first found that injecting IgG into mice from people suffering from long-term Covid-related pain, fatigue or both Decreased density of nerve fibers in the skinWhich is an indicator of nerve damage. Pain-related antibodies caused the mice to become hypersensitive to touch and cold.

Finally, Nikais and colleagues similarly found that mice injected with IgG from people with long-term COVID became more sensitive to touch. When they dissected the mice, they noticed that IgG had accumulated in the dorsal root ganglia, groups of neurons near the spinal cord that help transmit sensory information to the brain. The IgGs were localized around neurons that respond to pain and proprioception, the ability to sense the body’s own movement and position, which could lead to dizziness and vertigo.

Several steps will need to be taken to translate these results into treatments. The first thing to do is to find out which of the millions of types of IgG is causing the symptoms. Iwasaki’s team’s experiments identified two, which target proteins called MED20 and USP5.

It is also important to find out whether removing the autoantibodies or blocking their activity reduces symptoms. Brent Appelman At the Amsterdam University Medical Center in the Netherlands — who was part of Eijkelkamp’s team — is studying what happens when these autoantibodies, but not other substances, filtered from blood. Ejkelkamp emphasizes that apheresis is not a permanent solution, as you have to have it done in the hospital every few months. “It’s a perfect proof of concept,” says Ejkelkamp, ​​but he adds that the goal should be to become a drug.