Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar:93:415-419.
doi: 10.1016/j.bbi.2020.12.022. Epub 2020 Dec 24.

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

Christiana Franke  1 , Caroline Ferse  2 , Jakob Kreye  3 , S Momsen Reincke  4 , Elisa Sanchez-Sendin  5 , Andrea Rocco  6 , Mirja Steinbrenner  7 , Stefan Angermair  8 , Sascha Treskatsch  8 , Daniel Zickler  2 , Kai-Uwe Eckardt  2 , Rick Dersch  9 , Jonas Hosp  9 , Heinrich J Audebert  7 , Matthias Endres  10 , J Christoph Ploner  7 , Harald Prüß  11
Affiliations

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

Christiana Franke et al. Brain Behav Immun. 2021 Mar.

Abstract

Background: COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity.

Design: Blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies.

Results: Using cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb.

Conclusion: The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.

Keywords: Autoantibody; Autoimmunity; COVID-19; CSF; Encephalitis; Neurology; Viral-triggered.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
CSF of COVID-19 patients shows strong IgG autoreactivity on unfixed mouse brain sections. Representative images of indirect immunofluorescence demonstrate autoantibody binding to circumscribed anatomical structures including (A) neuropil of the olfactory bulb, (B) medium-sized vessels in the brain, (C) proximal dendrites of Purkinje neurons (arrowheads) and myelinated fibers (arrows) in the cerebellum, (D) neuropil in the hippocampus, (E) glia limitans (arrowheads) and astrocytes (enlarged box) throughout the brain. Several autoantibodies target intracellular antigens, such as (F) densely clustered intraneuronal epitopes, (G) perinuclear antigens or (H) nucleoli (arrowheads) as part of an anti-nuclear antibody response.
See this image and copyright information in PMC

Comment in

References

    1. Armangue T., Spatola M., Vlagea A., Mattozzi S., Carceles-Cordon M., Martinez-Heras E., Llufriu S., Muchart J., Erro M.E., Abraira L., Moris G., Monros-Gimenez L., Corral-Corral I., Montejo C., Toledo M., Bataller L., Secondi G., Arino H., Martinez-Hernandez E., Juan M., Marcos M.A., Alsina L., Saiz A., Rosenfeld M.R., Graus F., Dalmau J., Spanish Herpes Simplex Encephalitis Study G. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018;17:760–772. - PMC - PubMed
    1. Ropper A.H., Dalmau J., Graus F. Antibody-mediated encephalitis. N. Engl. J. Med. 2018;378(9):840–851. doi: 10.1056/NEJMra1708712. - DOI - PubMed
    1. Delamarre L., Gollion C., Grouteau G., Rousset D., Jimena G., Roustan J., Gaussiat F., Aldigé E., Gaffard C., Duplantier J., Martin C., Fourcade O., Bost C., Fortenfant F., Delobel P., Martin-Blondel G., Pariente J., Bonneville F., Geeraerts T. COVID-19–associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network. J. Neurol. Neurosurg. Psychiatry. 2020;91(9):1004–1006. doi: 10.1136/jnnp-2020-323678. - DOI - PMC - PubMed
    1. Eden A., Kanberg N., Gostner J., Fuchs D., Hagberg L., Andersson L.M., Lindh M., Price R.W., Zetterberg H., Gisslen M. CSF biomarkers in patients with COVID-19 and neurological symptoms: a case series. Neurology. 2020 - PubMed
    1. Fang B., McKeon A., Hinson S.R., Kryzer T.J., Pittock S.J., Aksamit A.J., Lennon V.A. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol. 2016;73(11):1297. doi: 10.1001/jamaneurol.2016.2549. - DOI - PubMed