A causal link between autoantibodies and neurological symptoms in long COVID 2133

Abstract Description Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a > 21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reporte Funding Sources This work was supported by the Else Kröner Fresenius Prize for Medical Research 2023, grants from the National Institute of Allergy and Infectious Diseases (R01AI157488 to A.I.), the Howard Hughes Medical Institute (A.I.). K.S.G.S. receive research support from Pew Latin American Fellowship. Topic Categories Neuroimmunology (NEUR)