Antibodies against SARS-CoV-2 spike protein in the cerebrospinal fluid of COVID-19 patients and vaccinated controls: a multicentre study.

Autor: Nersesjan V; Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. vardan.nersesjan@regionh.dk.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. vardan.nersesjan@regionh.dk., Boldingh MI; Department of Neurology, Oslo University Hospital, Oslo, Norway., Paulsen EQ; Department of Microbiology, Oslo University Hospital, Oslo, Norway., Argren M; Department of Neurology, Oslo University Hospital, Oslo, Norway., Høgestøl E; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Department of Psychology, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Aamodt AH; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Department of Neuromedicine and Movement Science, The Norwegian University of Science and Technology, Trondheim, Norway., Popperud TH; Department of Neurology, Oslo University Hospital, Oslo, Norway., Kondziella D; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Jørgensen CS; Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark., Jensen VVS; Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark., Benros ME; Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Dec 16; Vol. 272 (1), pp. 60. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1007/s00415-024-12769-4
Abstrakt: Introduction: SARS-CoV-2 antibodies in the cerebrospinal fluid (CSF) of COVID-19 patients possibly reflect blood-cerebrospinal fluid barrier (BCB) disruption due to systemic inflammation. However, some studies indicate that CSF antibodies signal a neurotropic infection. Currently, larger studies are needed to clarify this, and it is unknown if CSF antibodies appear solely after infection or also after COVID-19 vaccination. Therefore, we aimed to investigate the CSF dynamics of SARS-CoV-2 antibodies in a multicenter study of COVID-19 patients and vaccinated controls.
Methods: A cohort study of Danish and Norwegian COVID-19 patients and controls investigated with a lumbar puncture (April 2020-December 2022). Serum and CSF were analysed locally for routine investigations, and centrally at Statens Serum Institut (Danish governmental public health institute) for SARS-CoV-2 IgG antibodies against the spike protein using the Euroimmun (quantitative) and Wantai (qualitative) assays. Primary outcome was the quantity of CSF SARS-CoV-2 antibodies post-COVID versus post-vaccination. Secondary outcomes included regression models examining the relationship between CSF antibodies and serum levels, albumin ratio, CSF pleocytosis, COVID-19 severity, and temporal antibody dynamics.
Results: We included 124 individuals (Mean [SD] age 47.2 [16.6]; 59.7% males surviving COVID-19 and controls. Of these, 86 had paired CSF-serum testing. Antibody-index calculations did not support a SARS-CoV-2 brain infection. Multi-variate regression revealed that CSF SARS-CoV-2 antibodies were most strongly influenced by serum antibody levels and BCB permeability, as measured by increasing albumin ratio. CSF antibody levels displayed a dose-response relationship (p < 0.0001) influenced by preceding vaccinations or infections. CSF antibody levels (median [IQR]) were highest among those both previously infected and vaccinated, 100.0 [25.0-174.0], and those vaccinated without prior infection, 85.0 [12.0-142.0], and lowest among previously infected individuals without preceding vaccination, 5.9 [2.7-55.1], (p = 0.003). SARS-CoV-2 antibodies in CSF were also detected via qualitative assays in the COVID-19 (46.8%) and vaccinated (78.6%) groups, p = 0.03.
Conclusion: SARS-CoV-2 antibodies detected in CSF can be derived following both infection and vaccination for COVID-19. CSF antibody levels increase in a dose-response relationship with the number of prior infections and vaccinations and are most strongly influenced by serum antibody levels and BCB permeability. These findings stress the importance of carefully interpreting CSF antibody results when assessing neurological complications following infections not categorized as neurotropic.
Competing Interests: Declarations. Ethics approval and consent to participate: Written and informed consent was obtained from participants or legal next of kin. Data collection was approved by The Regional Committee on Health Research Ethics (j.no: H-20026602), the Danish Data Protection Agency (j.no: P-2020-497), and the Regional Ethics Committee for Medical Research in South Eastern Norway Health Authority (j.no: 152727 and 351097). Conflicts of interest: None.
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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