Publication date: May 28, 2026
Acute SARS-CoV-2 infection triggers the de novo production of diverse, functional autoantibodies (AABs) that remain elevated in long COVID (LC), but their pathogenic role remains unclear. Using tissue-based immunofluorescence, ELISA, human protein array, and mass spectrometry assays, we identified a broad range of AAB targets among individuals with LC. Individuals with neurocognitive symptoms showed increased AABs against central nervous system (CNS) and peripheral nervous system proteins. Purified immunoglobulin G (IgG) reacted with human locus coeruleus, thalamus, adrenal gland, and thyroid and cross-reacted with mouse sciatic nerve and meninges. CNS-reactive AABs correlated with several neurological symptoms. MED20-targeting IgG from patients with LC showed enhanced antibody-dependent phagocytosis. Passive transfer of IgG from individuals with LC into mice induced fatigue-like behavior, loss of balance/coordination, thermal hyperalgesia, small fiber nerve damage, and increased pain-related neuronal activity, recapitulating patients’ symptoms. These findings suggest that targeting AABs might offer therapeutic benefits for this LC subgroup.
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | long COVID |
| disease | MESH | SARS-CoV-2 infection |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | MESH | fatigue |
| drug | DRUGBANK | Isoxaflutole |
| disease | MESH | thermal hyperalgesia |
| disease | MESH | pain |
| disease | MESH | chronic pain |
| disease | MESH | infectious diseases |
| disease | MESH | Nervous System Diseases |
| disease | MESH | infection |
| disease | MESH | syndrome |
| disease | MESH | Post-Infectious Disorders |