New Study Links Long COVID to Autoimmune Attacks on Brain and Nerves

A new study reveals that antibodies from some long COVID patients may attack brain and nerve tissues, offering potential clues for future treatments.

Since the COVID-19 pandemic emerged in 2020, long COVID—a condition characterized by persistent and sometimes debilitating symptoms—has remained a medical mystery. Now, research co-led by Yale immunologist Akiko Iwasaki provides compelling evidence that, in certain patients, the immune system may turn against the body’s own cells, triggering symptoms such as fatigue, brain fog, and chronic pain.

The findings, published in the journal CELL, suggest that long COVID may share mechanisms with autoimmune diseases, even though it does not perfectly match any known condition. Iwasaki, a professor of immunobiology at Yale School of Medicine, emphasized that while the study identifies a potential autoimmune pathway, it does not explain all cases of long COVID.

“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.”

The research focused on autoantibodies—immune proteins that mistakenly target the body’s own tissues. By analyzing blood samples from long COVID patients, healthy volunteers, and individuals who recovered without lingering symptoms, the team discovered that autoantibodies in long COVID patients frequently attacked brain and nerve tissues. These included regions involved in pain signaling, memory, balance, and autonomic nervous system function, which could explain symptoms like brain fog, dizziness, and fatigue.

When the researchers exposed human and mouse tissues to purified antibodies from long COVID patients, they observed stronger reactions in brain and nerve tissues compared to control groups. Further screening against over 21,000 human proteins revealed that many targeted neurons, nerve communication pathways, inflammation, and hormone signaling.

To test the effects directly, the team transferred autoantibodies from long COVID patients into healthy mice. The mice developed increased pain sensitivity, fatigue, impaired balance, and damage to small nerve fibers. Behavioral studies also showed abnormal neuronal activation in brain regions linked to pain, 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 Keyla Santos Guedes de Sá, a postdoctoral associate in Iwasaki’s lab and lead author of the study.

The study builds on Iwasaki’s long-standing research into COVID immune responses. While long COVID has puzzled scientists since its emergence, the new findings provide some of the strongest evidence yet that autoimmunity may play a role in a subset of cases.

“When you dig into the literature, you see that every major pandemic is accompanied by a long-version, chronic illness that follows,” Iwasaki noted. “Many viral pathogens are capable of triggering these chronic diseases after infection.”

The researchers stress that much more work is needed to understand the mechanisms at play and to develop effective treatments. Currently, there is no approved therapy for long COVID, leaving patients without options.

“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,” de Sá said.

The study involved collaborators from Yale, Mount Sinai Health System, Howard Hughes Medical Institute, and institutions in Germany, and Berlin. While the findings offer a promising avenue for future research, Iwasaki and her team remain cautious about overstating the implications.

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

The research appears in CELL and was supported by multiple institutions, including the Howard Hughes Medical Institute and the National Institutes of Health.