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Cell
. 2026 May 28;189(11):3214-3235.e37.
doi: 10.1016/j.cell.2026.04.042.
A causal link between autoantibodies and neurological symptoms in long COVID
Keyla Santos Guedes de Sá 1 , Julio Silva 1 , Rafael Bayarri-Olmos 1 , Christopher A Baker 1 , Zhenni Lu 1 , Wilson Gipson 1 , Daxiang Na 2 , Bandy Chen 2 , Li Wenxue 3 , Delyar Khosroabadi 3 , Ryan Brinda 1 , Robert Alec Rath Constable 1 , Britney Omene 1 , Patricia A Colom Díaz 1 , Dong-Il Kwon 4 , Gisele Rodrigues 1 , Harald Heidecke 5 , Kai Schulze-Forster 5 , Amanda Gross 6 , Tom Shneer 6 , Amanda Clarke 6 , Thomas Linnekin 6 , Ashley Brate 6 , Lev Brown 6 , Henry Buda 6 , Shashi Jatiani 6 , Lenny Moise 6 , Kerrie Greene 1 , Sachin Bhagchandani 1 , Bornali Bhattacharjee 1 , Jeffrey Gehlhausen 1 , Jamie Wood 7 , Laura Tabacof 7 , Carmen Scheibenbogen 8 , Yansheng Liu 3 , Leying Guan 9 , Marc Schneeberger Pane 2 , David Putrino 10 , Tamas L Horvath 11 , Akiko Iwasaki 12
Affiliations
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.
Keywords: SARS-CoV-2; autoantibodies; behavior; chronic pain; infectious diseases; long COVID; nociceptor; post-acute infection syndrome.
. 2026 May 28;189(11):3214-3235.e37.
doi: 10.1016/j.cell.2026.04.042.
A causal link between autoantibodies and neurological symptoms in long COVID
Keyla Santos Guedes de Sá 1 , Julio Silva 1 , Rafael Bayarri-Olmos 1 , Christopher A Baker 1 , Zhenni Lu 1 , Wilson Gipson 1 , Daxiang Na 2 , Bandy Chen 2 , Li Wenxue 3 , Delyar Khosroabadi 3 , Ryan Brinda 1 , Robert Alec Rath Constable 1 , Britney Omene 1 , Patricia A Colom Díaz 1 , Dong-Il Kwon 4 , Gisele Rodrigues 1 , Harald Heidecke 5 , Kai Schulze-Forster 5 , Amanda Gross 6 , Tom Shneer 6 , Amanda Clarke 6 , Thomas Linnekin 6 , Ashley Brate 6 , Lev Brown 6 , Henry Buda 6 , Shashi Jatiani 6 , Lenny Moise 6 , Kerrie Greene 1 , Sachin Bhagchandani 1 , Bornali Bhattacharjee 1 , Jeffrey Gehlhausen 1 , Jamie Wood 7 , Laura Tabacof 7 , Carmen Scheibenbogen 8 , Yansheng Liu 3 , Leying Guan 9 , Marc Schneeberger Pane 2 , David Putrino 10 , Tamas L Horvath 11 , Akiko Iwasaki 12
Affiliations
- PMID: 42208499
- DOI: 10.1016/j.cell.2026.04.042
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.
Keywords: SARS-CoV-2; autoantibodies; behavior; chronic pain; infectious diseases; long COVID; nociceptor; post-acute infection syndrome.