Evidence map›Paper›PMID 35057809›Full record

ArticleJournal of neuroinflammation2022

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.

Sven Jarius, Florence Pache, Peter Körtvelyessy, Ilijas Jelčić, Mark Stettner, Diego Franciotta, Emanuela Keller, Bernhard Neumann, Marius Ringelstein, Makbule Senel and 28 more

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 2 pooled it
19.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.

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  10. Neuroimmune pathophysiology of long COVID.Psychiatry and clinical neurosciences · 2025
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31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 20 institutions in 5 countries.

Sven JariusMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
Florence PacheDepartment of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Peter KörtvelyessyDepartment of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Ilijas JelčićNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Mark StettnerDepartment of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University of Duisburg-Essen, Essen, Germany.
Diego FranciottaIRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Emanuela KellerNeurocritical Care Unit, Department of Neurosurgery and Institute of Intensive Care, University Hospital and University of Zurich, Zurich, Switzerland.
Bernhard NeumannDepartment of Neurology, University of Regensburg, Regensburg, Germany.
Marius RingelsteinDepartment of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Makbule SenelDepartment of Neurology, Ulm University, Ulm, Germany.
Axel RegeniterMedica Medical Laboratories Dr. F. Kaeppeli AG, Zurich, Switzerland.
Rea KalantzisDepartment of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Jan F WillmsInstitute of Intensive Care Medicine, University Hospital and University of Zurich, Zurich, Switzerland.
Achim BertheleDepartment of Neurology, School of Medicine, Technical University of Munich, Munich, Germany.
Markus BuschDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Marco CapobiancoRegional Referral Multiple Sclerosis Centre, Department of Neurology, University Hospital S. Luigi - Orbassano (I), Orbassano, Italy.
Amanda EiseleDepartment of Neurology, University Hospital Zurich, Zurich, Switzerland.
Ina ReichenNeuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Rick DerschClinic of Neurology and Neurophysiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sebastian RauerClinic of Neurology and Neurophysiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Katharina SandnerDepartment of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Ilya AyzenbergDepartment of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Catharina C GrossDepartment of Neurology with Institute of Translational Neurology, University and University Hospital Münster, Münster, Germany.
Harald HegenDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Michael KhalilDepartment of Neurology, Medical University of Graz, Graz, Austria.
Ingo KleiterDepartment of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Thorsten LenhardNeuroinfectiology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Jürgen HaasMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Orhan AktasDepartment of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Klemens AngstwurmDepartment of Neurology, University of Regensburg, Regensburg, Germany.
Christoph KleinschnitzDepartment of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University of Duisburg-Essen, Essen, Germany.
Jan LewerenzDepartment of Neurology, Ulm University, Ulm, Germany.
Hayrettin TumaniDepartment of Neurology, Ulm University, Ulm, Germany.
Friedemann PaulExperimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
Martin Stangel *Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hanover, Germany.
Klemens Ruprecht *Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Brigitte Wildemann *Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
in cooperation with the German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry
University Hospital of Zurich · CHHeidelberg University · DECharité - Universitätsmedizin Berlin · DEHeinrich Heine University Düsseldorf · DEMedizinische Hochschule Hannover · DEUniversität Ulm · DEUniversity of Duisburg-Essen · DEDeggendorf Institute of Technology · DEFachklinik für Neurologie Dietenbronn · DEFreie Universität Berlin · DEJohannes Gutenberg University Mainz · DEMax Delbrück Center · DEMedical University of Graz · ATOspedale Policlinico San Martino · ITOspedale San Luigi Gonzaga · ITRuhr University Bochum · DESt. Josef-Hospital · DETechnical University of Munich · DEUniversität Innsbruck · ATUniversity Hospital Münster · DE

Funding

Ministry for Education and Research Baden-Württemberg, Germany 1499 TG93 U1Swiss National Science Foundation 4078P0_198345
6 · The paper itself

Abstract

backgroundComprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far.

objectiveTo analyze systematically the CSF profile in COVID-19.

methodsRetrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers

resultsThe most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease.

conclusionsThe CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.

Indexed as

AdultBlood-Brain BarrierCerebrospinal Fluid ProteinsCOVID-19CytokinesEuropeFemaleHumansImmunity, CellularImmunoglobulin GLactic AcidLeukocyte CountMaleMiddle AgedNervous System DiseasesOligoclonal BandsCerebrospinal Fluid ProteinsCytokinesImmunoglobulin GLactic AcidOligoclonal BandsAntibody indexAutoantibodiesBlood-CSF barrierCentral nervous systemCerebrospinal fluid (CSF)Coronavirus disease 2019 (COVID-19)CytokinesEncephalitisEncephalopathyGuillain–Barré syndromeLumbar punctureNeurological symptomsOligoclonal bandsPolymerase Chain reaction (PCR)SARS-CoV-2 antibodiesSevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)

Identifiers

PMID35057809
PMCPMC8771621
OpenAlexW4205761474

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