When antibodies from long COVID patients were infused into healthy mice, something striking happened: every single animal that received antibodies from people with new-onset chronic pain developed pain behaviors of its own. That finding, from a Mount Sinai and Yale University research team, has cracked open one of the most puzzling mysteries of the pandemic—why millions of people continue to suffer debilitating symptoms months or even years after their initial COVID-19 infection.
The answer lies in autoimmunity: a misdirected immune system that, instead of clearing the virus and resetting, continues to attack the body's own tissues. Until now, doctors have had little scientific basis for understanding which long COVID patients might benefit from existing treatments, or even which patients harbored this particular subtype of the disease. That changes with this research, published in Cell.
Between 4% and 20% of COVID-19 survivors experience long COVID's constellation of symptoms—persistent fatigue, cognitive impairment, heart palpitations, joint and muscle pain—that can stretch on for months or years. The Mount Sinai–Yale team set out to untangle the different subtypes driving these symptoms by collecting and purifying antibodies from the blood of 87 long COVID participants and injecting them into mice. The results were unambiguous. "All animals infused with the antibodies from people with long COVID who had new-onset chronic pain as one of their symptoms went on to develop pain behaviors as a result of the infusion," says Akiko Iwasaki, a professor of immunobiology at Yale School of Medicine and co-senior author of the study.
This discovery opens a practical pathway: new-onset pain may be a reliable biomarker that flags which long COVID patients have autoantibodies driving their illness. "That suggested to us that new-onset pain is one of the most prominent signs that an individual with long COVID may have autoantibodies driving their symptoms," Iwasaki explains. "With further validation, this knowledge will help us in the future to quickly and accurately identify patients who may have this subset of long COVID."
David Putrino, director of the Cohen Center for Recovery From Complex Chronic Illness at Mount Sinai and co-senior author of the research, points out that existing therapies for autoimmune disorders could now be deployed with precision. Intravenous immunoglobulin (IVIG)—which contains antibodies from healthy donors and is used to treat conditions like lupus—has already been prescribed to some long COVID patients, but outcomes have been inconsistent. FcRn inhibitors, which lower antibody levels in the bloodstream, show similar promise. "Before, we had no way of predicting who would benefit from therapies like IVIG or FcRn inhibitors," Putrino says. "Our study now shows that if you are in a subgroup of long COVID patients who have autoantibodies circulating in your body, this is a quantifiable sign that you may be a good candidate."
On researchers' radar are additional approaches: CAR-T cell therapy, which could genetically modify a person's immune cells to target and eliminate those harmful antibody-secreting cells, and plasmapheresis, which filters autoantibodies directly from the blood. The significance runs deep. Long COVID has left millions searching for answers and relief. This research transforms autoimmunity from a hypothesis into a validated mechanism—one that finally allows clinicians to match treatments to patients most likely to benefit from them. That precision could reshape care for a generation of people still waiting to reclaim their health.