Study Points to Autoimmune Pathway Behind Long COVID Symptoms

Long COVID leaves many SARS-CoV-2 survivors with persistent fatigue, cognitive issues, palpitations, and musculoskeletal pain for months or years. Estimates cited in new research suggest 4%–20% of infected individuals continue to experience symptoms, with proposed mechanisms including viral persistence, latent virus reactivation, and immune dysregulation. Determining which pathways drive specific symptom clusters remains a diagnostic and therapeutic challenge.

Mount Sinai (New York, NY, USA) investigators, collaborating with Yale School of Medicine (New Haven, CT, USA), validated autoimmunity as a major contributor to symptom burden in some individuals with long COVID. The work, published in Cell on May 28, 2026 centers on the role of autoantibodies—antibodies that target the body's own tissues—and their link to neurological manifestations. The study pinpoints a patient subgroup in which immune attack appears to underlie ongoing symptoms.

Researchers collected and purified antibodies from the blood of 87 people with long COVID and infused them into healthy mice. All animals that received antibodies from donors who had new‑onset chronic pain developed pain behaviors after infusion. The pattern indicates a causal connection between circulating autoantibodies and pain, and it highlights new‑onset pain as a prominent sign of this autoantibody‑driven subset.

The findings also inform therapeutic stratification. Intravenous immunoglobulin (IVIG) is cited as a therapy commonly used for autoimmune disorders and already prescribed to some people with long COVID, as are FcRn inhibitors; however, responses have been inconsistent. The authors note that identifying patients with circulating autoantibodies could clarify which therapies are most likely to reduce symptom burden, and they list CAR‑T cell therapy and plasmapheresis among approaches under investigation.

The team also highlighted public health considerations for blood and plasma donation. They noted that long COVID is an exclusion criterion for donation in the U.K., while donation remains permitted in the U.S., and urged consideration of policy changes to better protect recipients.

“We've known for some time that long COVID involves not just one but a variety of phenotypes, and now we have validated that autoimmunity is a major contributor to the symptom burden. This new awareness of the physiology of long COVID will enable us to identify a number of effective treatments for autoimmunity that could significantly improve the symptoms of millions of people with this chronic condition,” said David Putrino, Ph.D., Nash Family Director of the Cohen Center for Recovery From Complex Chronic Illness at Mount Sinai and co‑senior author of the study.

“We learned that 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. 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. 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,” said Akiko Iwasaki, Ph.D., professor of immunobiology at Yale School of Medicine and co‑senior author.

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Icahn School of Medicine at Mount Sinai
Yale School of Medicine