A causal link between autoantibodies and neurological symptoms in Long COVID

• May 2026
• Cell

Publication Details

DOI: 10.1016/j.cell.2026.04.042

Abstract

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.

Authors

Keyla Santos Guedes de Sá, Julio Silva, Rafael Bayarri-Olmos, Christopher A Baker, Zhenni Lu, Wilson Gipson, Daxiang Na, Bandy Chen, Li Wenxue, Delyar Khosroabadi, Ryan Brinda, Robert Alec Rath Constable, Britney Omene, Patricia A Colom Díaz, Dong-Il Kwon, Gisele Rodrigues, Harald Heidecke, Kai Schulze-Forster, Amanda Gross, Tom Shneer, Amanda Clarke, Thomas Linnekin, Ashley Brate, Lev Brown, Henry Buda, Shashi Jatiani, Lenny Moise, Kerrie Greene, Sachin Bhagchandani, Bornali Bhattacharjee, Jeffrey Gehlhausen, Jamie Wood, Laura Tabacof, Carmen Scheibenbogen, Yansheng Liu, Leying Guan, Marc Schneeberger Pane, David Putrino, Tamas L Horvath, Akiko Iwasaki

Keywords

SARS-CoV-2; autoantibodies; behavior; chronic pain; infectious diseases; long COVID; nociceptor; post-acute infection syndrome