Yale study ties long COVID to autoimmune antibodies

autoantibodies in – A Yale-led study reports strong evidence that, in some long COVID patients, autoantibodies may be driving symptoms by mistakenly targeting parts of the brain and nervous system. Researchers found these antibodies reacted to neural tissue, screened them against

When Keyla Santos Guedes de Sá watched the mice react. it wasn’t just a lab result—it was a moment that looked like a story long COVID patients have been living for years. In the new Yale study. antibodies taken from long COVID patients were transferred into healthy mice. and the animals developed symptoms that mirrored what people report: increased pain sensitivity. fatigue. impaired balance. and damage to small nerve fibers.

The work. led by Yale researchers with collaborators including a Mount Sinai Health System team led by study co-senior author David Putrino. focuses on a specific immune clue—autoantibodies. These are immune proteins that are known to mistakenly target the body’s own tissues instead of viruses or bacteria. Since long COVID first emerged about six years ago. researchers have struggled to pin down causes because symptoms vary widely from person to person. The Yale team says the new findings offer some of the strongest evidence so far that autoimmunity may be an important factor for at least a subgroup.

The study zeroed in on what the antibodies were hitting. The researchers discovered that many long COVID patients had autoantibodies aimed at parts of the brain and nervous system. Their targets frequently involved tissues involved in pain signaling, memory, balance, sensory processing, and autonomic nervous system control. That pattern, the researchers said, could help explain symptoms such as brain fog, dizziness, headaches, fatigue, burning pain, and numbness.

To test whether those antibodies were behaving differently from others. the team analyzed blood samples from people with long COVID. healthy volunteers. and people who had recovered from COVID but had not developed lasting symptoms. The researchers purified antibodies from patients’ blood and exposed them to human and mouse tissues. finding that antibodies from long COVID patients reacted more strongly with certain brain regions and nerve tissues than antibodies from control groups.

Then came the broader search. The team screened these blood samples against more than 21,000 human proteins to identify what the antibodies were targeting. Many of the targets the researchers found were linked to neurons, nerve communication, inflammation, and hormone signaling.

In the mouse experiments, the antibodies didn’t just change behavior. Working with a team led by study co-senior author Tamas Horvath, the Jean and David W. Wallace Professor of Comparative Medicine. professor of neuroscience and of obstetrics. gynecology. and reproductive sciences at YSM. the researchers conducted various behavioral studies and observed the symptom changes. Working with Marc Schneeberger Pane. assistant professor in cellular and molecular physiology in Yale’s Faculty of Arts and Sciences. they also found abnormal neuronal activation in brain regions involved in pain. fatigue. memory. and emotional regulation.

“What was most fascinating about this work is that we were able to find antibodies that, when transferred to mice, caused the same type of symptoms that are reported by long COVID patients,” said study lead author Keyla Santos Guedes de Sá, a postdoctoral associate in immunobiology in Iwasaki’s lab.

The next question now becomes what, exactly, is doing the damage and how. The researchers said they will next examine how the damage is being done. “Now that we were able to identify a subgroup of patients whose condition might be driven by autoantibodies. we want to investigate the neurological and immunological mechanisms by which these autoantibodies are causing disease. ” Sá said.

That subgroup idea matters. because the lead investigator—Iwasaki. who has been a leading investigator on COVID immune response—stopped short of turning the study into a single explanation for everyone. “This is a significant finding, but that doesn’t mean there aren’t other causes,” Iwasaki said. “Our study does not explain the entire long COVID scenario. This is one possible cause of long COVID, but it will likely have other trigger causes as well.”.

She also pointed to a wider pattern she says researchers have seen in past pandemics. “When you dig into the literature. you see that every major pandemic is accompanied by a long-version. chronic illness that follows. ” Iwasaki added. “It happens when a human population is exposed to a new pathogen — or sometimes not even a new pathogen but an existing one like EBV [Epstein-Barr virus.] Many viral pathogens are capable of triggering these chronic diseases after infection.”.

For patients and clinicians, the most urgent question is still treatment. The researchers said that if the findings are eventually validated. the study could point toward future long COVID treatments. including therapies already used for other autoimmune diseases—though they stressed that much more investigation is needed.

“We’re all — Keyla and I and everybody in our team — driven by the desire to help people with long COVID,” Iwasaki said. “Right now, there is no approved treatment for these people, and they really need help.”

The study also included scientists from the Department of Immunobiology in YSM. the Center for Infection and Immunity. the Department of Comparative Medicine. the Department of Cellular and Molecular Physiology. and the Department of Pathology. Partners included researchers from the Yale Cancer Biology Institute on West Campus and from the Department of Biostatistics at the Yale School of Public Health.

Other collaborators named in the research included scientists from the Icahn School of Medicine at Mount Sinai. researchers from the Howard Hughes Medical Institute. Serom Yx Systems. CellTrend GmbH in Germany. and the Institute of Medical Immunology. Charité – Universitätsmedizin Berlin. Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin and Berlin Institute of Health.

Yale study long COVID autoantibodies autoimmune response brain and nervous system pain signaling brain fog fatigue dizziness small nerve fibers mouse experiments