Enhanced adenoviral reactivity in Guillain-Barré syndrome after SARS-CoV-2 infection and vaccination
Issued Date
2026-05-01
Resource Type
ISSN
00068950
eISSN
14602156
Scopus ID
2-s2.0-105037872036
Pubmed ID
41055073
Journal Title
Brain
Volume
149
Issue
5
Start Page
1718
End Page
1731
Rights Holder(s)
SCOPUS
Bibliographic Citation
Brain Vol.149 No.5 (2026) , 1718-1731
Suggested Citation
Bellanti R., Iserte A.C., Johnson C.B., Goodfellow J., Johnson M., Dejnirattisai W., Keddie S., Campo J.J., Screaton G., Goldblatt D., Lunn M.P., Davies A.J., Rinaldi S. Enhanced adenoviral reactivity in Guillain-Barré syndrome after SARS-CoV-2 infection and vaccination. Brain Vol.149 No.5 (2026) , 1718-1731. 1731. doi:10.1093/brain/awaf376 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116673
Title
Enhanced adenoviral reactivity in Guillain-Barré syndrome after SARS-CoV-2 infection and vaccination
Author's Affiliation
University of Oxford Medical Sciences Division
UCL Queen Square Institute of Neurology
UCL Great Ormond Street Institute of Child Health
Nuffield Department of Medicine
The Royal London Hospital
Siriraj Hospital
Queen Elizabeth University Hospital, Glasgow
Centro Tecnológico Leitat
Antigen Discovery Inc.
UCL Queen Square Institute of Neurology
UCL Great Ormond Street Institute of Child Health
Nuffield Department of Medicine
The Royal London Hospital
Siriraj Hospital
Queen Elizabeth University Hospital, Glasgow
Centro Tecnológico Leitat
Antigen Discovery Inc.
Corresponding Author(s)
Other Contributor(s)
Abstract
Case reports and series suggested an association between SARS-CoV-2 and Guillain-Barré syndrome (GBS). However, the GBS epidemic which was predicted from early risk estimates did not materialize in overall case numbers, and no plausible mechanism for any link has been established. An increased risk of GBS following adenoviral vector-based COVID-19 vaccination has been more consistently demonstrated, but a pathophysiological explanation for this association has also not yet emerged. Here, we sought to identify whether patients with GBS following COVID-19 infection or vaccination had any distinct clinical or serological features differentiating them from one another or non-pandemic GBS, and to explore the potential mechanisms of any associations. Between March 2020 and October 2021, sera from patients with GBS (n = 64) and controls (n = 70) were collected. Clinical features were retrieved from medical records. GBS cases were evaluated for diagnostic certainty by Brighton criteria and classified as non-COVID-19 associated (GBS-NC, n = 20), GBS after COVID-19 infection (GBS-AC, n = 10), or GBS after COVID-19 vaccination (GBS-AV, n = 34). The humoral responses to SARS-CoV-2 proteins and putative peripheral nerve antigens, and the cytokine profile of each group were established and compared. Antibodies cloned from the acute-phase plasmablasts of an individual with GBS-AC were also assessed for reactivity against SARS-CoV-2 and peripheral nerve antigens. Sera from GBS patients and from individuals who received COVID-19 vaccinations (n = 36: 16 ChAdOx1, 10 Ad26.COV2.S/Janssen and 10 tozinameran/Pfizer–BioNTech) without developing GBS were tested for IgG reactivity against SARS-CoV-2 and adenoviral proteins. There were no clinical differences between the GBS groups. Patients with GBS-AC had a greater IgG reactivity to the S1 component of the SARS-CoV-2 spike protein compared to non-GBS COVID-19 controls. A minority of antibodies from cloned plasmablasts targeted SARS-CoV-2 proteins but there was no reactivity or cross reactivity with peripheral nerve antigens or tissue. There were no other serological or immunological differences between the GBS groups. However, when compared to uncomplicated vaccine recipients, GBS patients in toto, and each group individually, demonstrated significantly greater antibody reaction to a range of human adenoviral proteins. Compared to controls exposed to the same immunological stimulus, antibody reactivities to viral antigens are enhanced in patients with GBS. However, we found no mechanistic link between S1 and peripheral nerve reactivity or pathology. Serological responses to adenoviral proteins may be directly involved in the pathogenesis of Guillain-Barré syndrome, potentially contributing to cases with currently unexplained aetiology.