Attacks of our immune system are the cause of long covid

Evidence is mounting that prolonged covid may be caused by the immune system attacking the body. The results of the 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 when pain is the primary symptom.

This could one day lead to a treatment sorely lacking in long covid; there are no approved therapies in the UK or US. “We have to take the antibodies away from the patients and see if the symptoms go away,” he 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 months or even years. These vary enormously, but the most common include fatigue, pain, brain fog, and post-exercise sickness, where even moderate activity leads to exhaustion.

Scientists have identified a number of mechanisms that may contribute to long-term covid, including SARS-CoV-2 persisting in the body and gut microbiome dysfunction. One or more of these mechanisms may be at work in any person with long covid, which may explain both the range of symptoms and the difficulty in finding widely applicable treatments.

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

The first hint that autoantibodies contribute to long covid came in 2023, when scientists filtered the blood of people with long covid using a technique called apheresis. This was associated with lower levels of autoantibodies and improvement in symptoms, but so many substances were filtered out that it was impossible to determine which were responsible.

Now Eijkelkamp and his colleagues have presented evidence that autoantibodies can indeed cause some lingering covid symptoms. Starting in 2022, they studied 34 people with the disease plus 15 control subjects who were infected with SARS-CoV-2 but did not develop covid for a long time. The team focused on a highly prevalent set of antibodies called immunoglobulin G (IgG) in the blood of the participants they injected into the mice.

When these antibodies came from people with long covid, the mice became more sensitive to touch, even tender and painful. They also pulled the paw away from the hot surface faster than the controls. The increased sensitivity to pain matches what we see in some people with long covid, says Eijkelkamp.

When the team repeated the experiment in 2024 using IgG from 19 participants who still had long covid, they saw the same effects. “These autoantibodies persist in patients’ bodies,” he says Charles Nicaise at the University of Namur in Belgium, who participated in another of the four studies.

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

First headed by Akiko Iwasaki at Yale University and published in July 2024, similarly found that people with long covid had high levels of autoantibodies in their bloodand that those with neurological symptoms had autoantibodies that targeted proteins in the nervous system. Transferring these mice to mice similarly made them more sensitive to touch and pain and began to have difficulty with balance and coordination, similar to how people with long covid sometimes experience dizziness.

The remaining two studies were published in November 2025. The first found that injecting IgG from humans with chronic pain related to covid, fatigue or both into mice reduces the density of nerve fibers in the skinindicating nerve damage. The pain-related antibodies also made the mice hypersensitive to touch and cold.

Finally, Nicaise and his colleagues similarly found that mice received injections of IgG from humans with long covid became more sensitive to touch. When they dissected the mice, they saw that IgG had accumulated in the dorsal root ganglia, clusters of neurons near the spinal cord that help transmit sensory information to the brain. The IgGs were localized around neurons that responded to pain and proprioception, the body’s ability to sense its own movement and position, which could lead to dizziness and vertigo.

In order for these results to become a treatment, several steps must be taken. The first is to find out which of the millions of IgG types is causing the symptoms. Iwasaki’s team’s experiments identified two that target proteins called MED20 and USP5.

It is also important to see if removing autoantibodies or blocking their activity alleviates symptoms. Brent Appelman at 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 out of the blood. Eijkelkamp stresses that apheresis is not a permanent solution, as you have to have it done every few months in a hospital. “This is a perfect proof of concept,” says Eijkelkamp, ​​but adds that the target should be the drug.

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