Emerging research strongly suggests that long COVID may, in some cases, be driven by the body’s own immune system turning against itself. Four recent studies indicate that autoimmunity—where antibodies mistakenly attack healthy tissues—contributes to lingering symptoms, particularly pain. This is a critical finding because it points toward potential, targeted treatments for a condition that currently lacks approved therapies in countries like the UK and US.
The Autoimmune Connection
Most people recover from SARS-CoV-2 infection within days. However, a significant portion experience persistent symptoms like fatigue, pain, brain fog, and post-exertional malaise. While several mechanisms may be at play—including lingering virus fragments and gut microbiome imbalances—the growing body of evidence focuses on autoantibodies. These antibodies, normally meant to bind to pathogens for elimination, sometimes misfire and attack the body’s own cells.
Early indications of this autoimmune link came from apheresis studies in 2023, where filtering blood reduced autoantibody levels and improved symptoms. However, the non-specific nature of the filtering made it difficult to pinpoint which antibodies were responsible. More recent research now narrows the focus.
Experimental Evidence: Antibodies Transfer Pain
Researchers led by Niels Eijkelkamp at Utrecht University began in 2022 by injecting immunoglobulin G (IgG) antibodies extracted from people with long COVID into mice. The results were striking: mice became more sensitive to touch and pain, retracting paws from hot surfaces faster than control mice. Repeating the experiment in 2024 with a new cohort confirmed these effects, demonstrating persistent autoantibody presence in long COVID patients.
Similar findings emerged from independent studies. Akiko Iwasaki at Yale University found high levels of autoantibodies in long COVID patients, with neurological symptoms correlating to antibodies targeting the nervous system. Transferring these antibodies into mice induced touch hypersensitivity, pain, and impaired coordination. Another study showed injected IgGs reduced nerve fiber density in mice, suggesting nerve damage. A final study located the antibodies in dorsal root ganglia near the spinal cord, disrupting pain and proprioception (body awareness).
Future Treatments: Targeting Specific Antibodies
The next step involves identifying which IgGs are driving symptoms. Iwasaki’s team has already pinpointed two targets: proteins called MED20 and USP5. Further research, including ongoing work by Brent Appelman at Amsterdam University Medical Centre, focuses on isolating and removing these specific autoantibodies. While apheresis offers short-term relief, the ultimate goal is a pharmaceutical intervention.
“This is a perfect proof of concept,” says Eijkelkamp. “But the aim should be a drug.”
This research represents a significant leap toward understanding the complex pathology of long COVID. By identifying the autoimmune mechanisms at play, scientists are paving the way for targeted therapies that could finally provide relief to millions suffering from persistent symptoms.
