Cell
Autoantibodies may drive neurologic symptoms in long COVID
Clinical Takeaway: Consider that a subset of patients with long COVID may have an autoantibody-driven disease process. Biomarker-based identification of these patients could help guide future use of therapies such as IVIG, FcRn inhibitors, plasmapheresis, or other immune-targeted approaches.
Long COVID affects an estimated 4% to 20% of people after SARS-CoV-2 infection and can cause persistent symptoms such as fatigue, cognitive impairment, pain, and dizziness. Although immune dysfunction has long been suspected, the underlying drivers remain unclear, limiting treatment options. Identifying a specific autoimmune mechanism could help clinicians better classify patients and guide use of targeted therapies.
Investigators from Mount Sinai, Yale, and collaborating institutions found evidence that autoantibodies may be a causal driver of neurologic symptoms in some patients with long COVID. Researchers analyzed blood samples from 87 participants with long COVID and compared findings with healthy and post-COVID controls.
Using a protein array containing more than 21,000 human proteins, the team identified a broad range of autoantibodies enriched in patients with neurocognitive symptoms. Among 55 participants with a high neurologic symptom burden, 80% reported brain fog, 65% headaches, 64% memory loss, 58% dizziness, and 58% sleep disturbances. Autoantibodies frequently targeted proteins in the central and peripheral nervous systems and showed reactivity against human brain tissue as well as mouse neural tissues.
To test whether the antibodies were pathogenic, investigators transferred purified IgG from patients into healthy mice. The animals subsequently developed pain hypersensitivity, impaired balance and coordination, and other neurologic abnormalities that mirrored symptoms reported by the antibody donors, supporting a causal role for the antibodies rather than a simple association.
“We have validated that autoimmunity is a major contributor to the symptom burden,” said co-senior author David Putrino, PhD. He added that identifying patients with circulating autoantibodies could help predict who is most likely to respond to therapies such as IVIG or FcRn inhibitors. The authors note that long COVID remains biologically heterogeneous, and autoimmunity is likely one of several mechanisms underlying persistent symptoms.
Source: Santos Guedes de Sa K, et al. (2026, May 28). Cell. A causal link between autoantibodies and neurological symptoms in long COVID