tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Julio Silva[SUP] 1 [/SUP], Rafael Bayarri-Olmos[SUP] 1 [/SUP], Christopher A Baker[SUP] 1 [/SUP], Zhenni Lu[SUP] 1 [/SUP], Wilson Gipson[SUP] 1 [/SUP], Daxiang Na[SUP] 2 [/SUP], Bandy Chen[SUP] 2 [/SUP], Li Wenxue[SUP] 3 [/SUP], Delyar Khosroabadi[SUP] 3 [/SUP], Ryan Brinda[SUP] 1 [/SUP], Robert Alec Rath Constable[SUP] 1 [/SUP], Britney Omene[SUP] 1 [/SUP], Patricia A Colom Díaz[SUP] 1 [/SUP], Dong-Il Kwon[SUP] 4 [/SUP], Gisele Rodrigues[SUP] 1 [/SUP], Harald Heidecke[SUP] 5 [/SUP], Kai Schulze-Forster[SUP] 5 [/SUP], Amanda Gross[SUP] 6 [/SUP], Tom Shneer[SUP] 6 [/SUP], Amanda Clarke[SUP] 6 [/SUP], Thomas Linnekin[SUP] 6 [/SUP], Ashley Brate[SUP] 6 [/SUP], Lev Brown[SUP] 6 [/SUP], Henry Buda[SUP] 6 [/SUP], Shashi Jatiani[SUP] 6 [/SUP], Lenny Moise[SUP] 6 [/SUP], Kerrie Greene[SUP] 1 [/SUP], Sachin Bhagchandani[SUP] 1 [/SUP], Bornali Bhattacharjee[SUP] 1 [/SUP], Jeffrey Gehlhausen[SUP] 1 [/SUP], Jamie Wood[SUP] 7 [/SUP], Laura Tabacof[SUP] 7 [/SUP], Carmen Scheibenbogen[SUP] 8 [/SUP], Yansheng Liu[SUP] 3 [/SUP], Leying Guan[SUP] 9 [/SUP], Marc Schneeberger Pane[SUP] 2 [/SUP], David Putrino[SUP] 10 [/SUP], Tamas L Horvath[SUP] 11 [/SUP], Akiko Iwasaki[SUP] 12 [/SUP]
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[SUP] 1 [/SUP], Julio Silva[SUP] 1 [/SUP], Rafael Bayarri-Olmos[SUP] 1 [/SUP], Christopher A Baker[SUP] 1 [/SUP], Zhenni Lu[SUP] 1 [/SUP], Wilson Gipson[SUP] 1 [/SUP], Daxiang Na[SUP] 2 [/SUP], Bandy Chen[SUP] 2 [/SUP], Li Wenxue[SUP] 3 [/SUP], Delyar Khosroabadi[SUP] 3 [/SUP], Ryan Brinda[SUP] 1 [/SUP], Robert Alec Rath Constable[SUP] 1 [/SUP], Britney Omene[SUP] 1 [/SUP], Patricia A Colom Díaz[SUP] 1 [/SUP], Dong-Il Kwon[SUP] 4 [/SUP], Gisele Rodrigues[SUP] 1 [/SUP], Harald Heidecke[SUP] 5 [/SUP], Kai Schulze-Forster[SUP] 5 [/SUP], Amanda Gross[SUP] 6 [/SUP], Tom Shneer[SUP] 6 [/SUP], Amanda Clarke[SUP] 6 [/SUP], Thomas Linnekin[SUP] 6 [/SUP], Ashley Brate[SUP] 6 [/SUP], Lev Brown[SUP] 6 [/SUP], Henry Buda[SUP] 6 [/SUP], Shashi Jatiani[SUP] 6 [/SUP], Lenny Moise[SUP] 6 [/SUP], Kerrie Greene[SUP] 1 [/SUP], Sachin Bhagchandani[SUP] 1 [/SUP], Bornali Bhattacharjee[SUP] 1 [/SUP], Jeffrey Gehlhausen[SUP] 1 [/SUP], Jamie Wood[SUP] 7 [/SUP], Laura Tabacof[SUP] 7 [/SUP], Carmen Scheibenbogen[SUP] 8 [/SUP], Yansheng Liu[SUP] 3 [/SUP], Leying Guan[SUP] 9 [/SUP], Marc Schneeberger Pane[SUP] 2 [/SUP], David Putrino[SUP] 10 [/SUP], Tamas L Horvath[SUP] 11 [/SUP], Akiko Iwasaki[SUP] 12 [/SUP]
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.