Attacks from our immune system are a cause of long covid

Evidence is mounting that long covid can 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, particularly if pain is a primary symptom.

This could one day lead to treatments, which are sorely lacking for long covid; there are no approved therapies in the UK or the US. “We have to take the antibodies away in patients and see if the symptoms go away,” says Niels Eijkelkamp at Utrecht University in the Netherlands.

While most people infected by 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 ones include fatigue, pain, brain fog and post-exertional malaise, in which even mild activity leads to exhaustion.

Researchers have identified a host of mechanisms that may contribute to long covid, including SARS-CoV-2 persisting in the body and dysfunction of the gut microbiome. In any one person with 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 broadly 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 molecules on pathogens, which can then be targeted for destruction, but sometimes the immune system makes a mistake and creates “autoantibodies” that bind to the body’s cells.

An early hint that autoantibodies contribute to long covid came in 2023, when researchers filtered the blood of people with long covid using a technique called apheresis. This was associated with lower levels of autoantibodies and improved symptoms, but so many substances were filtered out that it wasn’t possible to determine which ones were responsible.

Now, Eijkelkamp and his colleagues have produced evidence that autoantibodies really could cause some long covid symptoms. Beginning in 2022, they studied 34 people with the condition, plus 15 control subjects who had been infected with SARS-CoV-2 but didn’t 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 covid, the mice became more sensitive to touch, even gentle, and pain. They also pulled their paw away from a hot surface more quickly than the controls. Increased pain sensitivity matches what we see in some people with long covid, says Eijkelkamp.

When the team repeated the experiment in 2024, using IgGs from 19 of the participants who still had long covid, they saw the same effects. “There is a persistence of these autoantibodies in the bodies of the patients,” says Charles Nicaise at the University of Namur in Belgium, who was involved in another of the four studies.

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

The first, led by Akiko Iwasaki at Yale University and released in July 2024, similarly found that people with long covid had high levels of autoantibodies in their blood, and that those with neurological symptoms had autoantibodies that targeted proteins in the nervous system. Transferring these into mice similarly made them more sensitive to touch and pain, and they started to struggle with balance and coordination, much like people with long covid sometimes experiencing dizziness.

The remaining two studies were released in November 2025. The first found that injecting IgGs from people with long covid-related pain, fatigue or both into mice reduced the density of nerve fibres in the skin, which is suggestive of nerve damage. The pain-related antibodies also caused the mice to become hypersensitive to touch and cold.

Finally, Nicaise and his colleagues similarly found that mice injected with IgGs from people with long covid became more sensitive to touch. When they dissected the mice, they saw that the IgGs 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 localised 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.

To turn these results into a treatment, several steps must be taken. The first is to spot which of the millions of types of IgGs are causing the symptoms. Experiments by Iwasaki’s team identified two, which target proteins called MED20 and USP5.

It’s also crucial to find out if removing the autoantibodies or blocking their activity alleviates symptoms. Brent Appelman at Amsterdam University Medical Centre in the Netherlands – who was part of Eijkelkamp’s team – is studying what happens when these autoantibodies, but not other substances, are filtered out of the blood. Eijkelkamp emphasises that apheresis isn’t a permanent solution, because you need to have it done every few months in hospital. “This is a perfect proof of concept,” says Eijkelkamp, but he adds that the aim should be a drug.