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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Guillain-Barré Syndrome | Research

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

Authors: Sven Jarius, Florence Pache, Peter Körtvelyessy, Ilijas Jelčić, Mark Stettner, Diego Franciotta, Emanuela Keller, Bernhard Neumann, Marius Ringelstein, Makbule Senel, Axel Regeniter, Rea Kalantzis, Jan F. Willms, Achim Berthele, Markus Busch, Marco Capobianco, Amanda Eisele, Ina Reichen, Rick Dersch, Sebastian Rauer, Katharina Sandner, Ilya Ayzenberg, Catharina C. Gross, Harald Hegen, Michael Khalil, Ingo Kleiter, Thorsten Lenhard, Jürgen Haas, Orhan Aktas, Klemens Angstwurm, Christoph Kleinschnitz, Jan Lewerenz, Hayrettin Tumani, Friedemann Paul, Martin Stangel, Klemens Ruprecht, Brigitte Wildemann, in cooperation with the German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

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

Objective

To analyze systematically the CSF profile in COVID-19.

Methods

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

Results

The 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.

Conclusions

The 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.
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Literature
1.
Leonardi M, Padovani A, McArthur JC. Neurological manifestations associated with COVID-19: a review and a call for action. J Neurol. 2020;267:1573–6.PubMedCrossRefPubMedCentral
2.
Chen X, Laurent S, Onur OA, Kleineberg NN, Fink GR, Schweitzer F, Warnke C. A systematic review of neurological symptoms and complications of COVID-19. J Neurol. 2021;268:392–402.PubMedCrossRef
3.
Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, Zandi MS, Lewis G, David AS. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7:611–27.PubMedPubMedCentralCrossRef
4.
Fuchs V, Kutza M, Wischnewski S, Deigendesch N, Lutz L, Kulsvehagen L, Ricken G, Kappos L, Tzankov A, Hametner S, et al. Presence of SARS-CoV-2 transcripts in the choroid plexus of ms and non-ms patients with COVID-19. Neurol Neuroimmunol Neuroinflamm 2021;8:e957.PubMedPubMedCentralCrossRef
5.
Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, Laue M, Schneider J, Brunink S, Greuel S, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24:168–75.PubMedCrossRef
6.
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021.
7.
Alexopoulos H, Magira E, Bitzogli K, Kafasi N, Vlachoyiannopoulos P, Tzioufas A, Kotanidou A, Dalakas MC. Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients. Neurol Neuroimmunol Neuroinflamm 2020;7:e893.PubMedPubMedCentralCrossRef
8.
Bodro M, Compta Y, Llanso L, Esteller D, Doncel-Moriano A, Mesa A, Rodriguez A, Sarto J, Martinez-Hernandez E, Vlagea A, et al. Increased CSF levels of IL-1beta, IL-6, and ACE in SARS-CoV-2-associated encephalitis. Neurol Neuroimmunol Neuroinflamm 2020;7:e821.PubMedPubMedCentralCrossRef
9.
Tandon M, Kataria S, Patel J, Mehta TR, Daimee M, Patel V, Prasad A, Chowdhary AA, Jaiswal S, Sriwastava S. A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19. Int J Infect Dis. 2021;104:390–7.PubMedPubMedCentralCrossRef
10.
Tuma RL, Guedes BF, Carra R, Iepsen B, Rodrigues J, Camelo-Filho AE, Kubota G, Ferrari M, Studart-Neto A, Oku MH, et al. Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series. Neurol Sci. 2021;42:479–89.PubMedCrossRef
11.
Lewis A, Frontera J, Placantonakis DG, Lighter J, Galetta S, Balcer L, Melmed KR. Cerebrospinal fluid in COVID-19: a systematic review of the literature. J Neurol Sci. 2021;421:117316.PubMedPubMedCentralCrossRef
12.
Lersy F, Benotmane I, Helms J, Collange O, Schenck M, Brisset JC, Chammas A, Willaume T, Lefebvre N, Solis M, et al. Cerebrospinal fluid features in patients with coronavirus disease 2019 and neurological manifestations: correlation with brain magnetic resonance imaging findings in 58 patients. J Infect Dis. 2021;223:600–9.PubMedCrossRef
13.
Jarius S, Pellkofer H, Siebert N, Korporal-Kuhnke M, Hummert MW, Ringelstein M, Rommer PS, Ayzenberg I, Ruprecht K, Klotz L, et al. Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients. J Neuroinflammation. 2020;17:261.PubMedPubMedCentralCrossRef
14.
Jarius S, Lechner C, Wendel EM, Baumann M, Breu M, Schimmel M, Karenfort M, Marina AD, Merkenschlager A, Thiels C, et al. Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 2: Results from 108 lumbar punctures in 80 pediatric patients. J Neuroinflammation. 2020;17:262.PubMedPubMedCentralCrossRef
15.
Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, Rommer P, Kleiter I, Stich O, Reuss R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011;306:82–90.PubMedCrossRef
16.
Jarius S, Konig FB, Metz I, Ruprecht K, Paul F, Bruck W, Wildemann B. Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis. J Neuroinflammation. 2017;14:171.PubMedPubMedCentralCrossRef
17.
Jarius S, Wurthwein C, Behrens JR, Wanner J, Haas J, Paul F, Wildemann B. Balo’s concentric sclerosis is immunologically distinct from multiple sclerosis: results from retrospective analysis of almost 150 lumbar punctures. J Neuroinflammation. 2018;15:22.PubMedPubMedCentralCrossRef
18.
Jarius S, Haas J, Paul F, Wildemann B. Myelinoclastic diffuse sclerosis (Schilder’s disease) is immunologically distinct from multiple sclerosis: results from retrospective analysis of 92 lumbar punctures. J Neuroinflammation. 2019;16:51.PubMedPubMedCentralCrossRef
19.
Tumani H, Petereit H-F: Leitlinie Lumbalpunktion und Liquordiagnostik, S1-Leitlinie, 2019, in: Deutsche Gesellschaft für Liquordiagnostik und Klinische Neurochemie (Hrsg.), Leitlinien für Diagnostik und Therapie in der Neurologie. Online: www.​dgn.​org/​leitlinien. abgerufen am 07 May 2020.
20.
Petereit HF, Sindern E, Wick M. [CSF diagnostics. Guidelines and catalogue of methods of the German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry]. Heidelberg: Springer; 2007.
21.
Tumani H, Petereit HF, Gerritzen A, Gross CC, Huss A, Isenmann S, Jesse S, Khalil M, Lewczuk P, Lewerenz J, et al. S1 guidelines “lumbar puncture and cerebrospinal fluid analysis” (abridged and translated version). Neurol Res Pract. 2020;2:8.PubMedPubMedCentralCrossRef
22.
Andersson M, Alvarez-Cermeno J, Bernardi G, Cogato I, Fredman P, Frederiksen J, Fredrikson S, Gallo P, Grimaldi LM, Gronning M, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry. 1994;57:897–902.PubMedPubMedCentralCrossRef
23.
Reiber H. Cerebrospinal fluid–physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler. 1998;4:99–107.PubMed
24.
Reiber H, Ungefehr S, Jacobi C. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler. 1998;4:111–7.PubMedCrossRef
25.
Reiber H. Flow rate of cerebrospinal fluid (CSF)–a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994;122:189–203.PubMedCrossRef
26.
Kuzior H, Fiebich BL, Yousif NM, Saliba SW, Ziegler C, Nickel K, Maier SJ, Suss P, Runge K, Matysik M, et al. Increased IL-8 concentrations in the cerebrospinal fluid of patients with unipolar depression. Compr Psychiatry. 2020;102:152196.PubMedCrossRef
27.
Cao Y, Tao X, Xu M. Value of cerebrospinal fluid IL-8 and IFN-γ level in early diagnosis of tuberculous meningitis and evaluation of prognosis. Acta Medica Mediterranea. 2020;36:2875.
28.
Kaminska J, Lyson T, Chrzanowski R, Sawicki K, Milewska AJ, Tylicka M, Zinczuk J, Matowicka-Karna J, Dymicka-Piekarska V, Mariak Z, Koper-Lenkiewicz OM. Ratio of IL-8 in CSF versus Serum Is Elevated in Patients. J Clin Med. 2020;9:1761.PubMedCentralCrossRef
29.
Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, Fritzinger M, Horn P, Vajkoczy P, Kreisel S, et al. Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry. 2001;70:534–7.PubMedPubMedCentralCrossRef
30.
Postal M, Ruocco HH, Brandao CO, Costallat LTL, Silva L, Cendes F, Appenzeller S. Interferon-gamma Is Associated with Cerebral Atrophy in Systemic Lupus Erythematosus. NeuroImmunoModulation. 2017;24:100–5.PubMedCrossRef
31.
Zaremba J, Losy J. Early TNF-alpha levels correlate with ischaemic stroke severity. Acta Neurol Scand. 2001;104:288–95.PubMedCrossRef
32.
Glimaker M, Kragsbjerg P, Forsgren M, Olcen P. Tumor necrosis factor-alpha (TNF alpha) in cerebrospinal fluid from patients with meningitis of different etiologies: high levels of TNF alpha indicate bacterial meningitis. J Infect Dis. 1993;167:882–9.PubMedCrossRef
33.
Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994;165:208–10.PubMedCrossRef
34.
Starhof C, Winge K, Heegaard NHH, Skogstrand K, Friis S, Hejl A. Cerebrospinal fluid pro-inflammatory cytokines differentiate parkinsonian syndromes. J Neuroinflammation. 2018;15:305.PubMedPubMedCentralCrossRef
35.
Wildemann B, Oschmann P, Reiber H. Laboratory diagnosis in neurology. Stuttgart: Thieme; 2011.
36.
Wurster U, Stachan R, Windhagen A, Petereit HF, Leweke FM. Reference values for standard cerebrospinal fluid examinations in multiple sclerosis. Results from 99 healthy volunteers. Mult Scler. 2006;12:P248.
37.
Schwenkenbecher P, Janssen T, Wurster U, Konen FF, Neyazi A, Ahlbrecht J, Puppe W, Bonig L, Suhs KW, Stangel M, et al. The influence of blood contamination on cerebrospinal fluid diagnostics. Front Neurol. 2019;10:584.PubMedPubMedCentralCrossRef
38.
Abela I, Pasin C, Schwarzmüller M, Epp S, Sickmann M, Schanz M, Rusert P, Weber J, Schmutz S, Audigé A, et al. Multifactorial SARS-CoV-2 seroprofiling dissects interdependencies with human coronaviruses and predicts neutralization activity. Nat Commun 2021;12:6703.PubMedPubMedCentralCrossRef
39.
Jarius S, Eichhorn P, Franciotta D, Petereit HF, Akman-Demir G, Wick M, Wildemann B. The MRZ reaction as a highly specific marker of multiple sclerosis: re-evaluation and structured review of the literature. J Neurol. 2017;264:453–66.PubMedCrossRef
40.
41.
Hermetter C, Fazekas F, Hochmeister S. Systematic review: syndromes, early diagnosis, and treatment in autoimmune encephalitis. Front Neurol. 2018;9:706.PubMedPubMedCentralCrossRef
42.
Jarius S, Probst C, Borowski K, Franciotta D, Wildemann B, Stoecker W, Wandinger KP. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J Neurol Sci. 2010;291:52–6.PubMedCrossRef
43.
Jarius S, Wildemann B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol. 2013;23:661–83.PubMedPubMedCentralCrossRef
44.
Reiber H, Zeman D, Kusnierova P, Mundwiler E, Bernasconi L. Diagnostic relevance of free light chains in cerebrospinal fluid—The hyperbolic reference range for reliable data interpretation in quotient diagrams. Clin Chim Acta. 2019;497:153–62.PubMedCrossRef
45.
Schwenkenbecher P, Konen FF, Wurster U, Witte T, Gingele S, Suhs KW, Stangel M, Skripuletz T. Reiber’s diagram for kappa free light chains: the new standard for assessing intrathecal synthesis? Diagnostics (Basel). 2019;9:194.CrossRef
46.
Kestner M, Rosler AE, Baumgärtner M, Lindner A, Orth M. CSF interleukin 6—a useful biomarker of meningitis in adults?/Liquor Interleukin 6—a ein sinnvoller Biomarker für die Meningitis beim Erwachsenen. J Lab Med. 2011;35:107–13.
47.
Espindola OM, Siqueira M, Soares CN, Lima M, Leite A, Araujo AQC, Brandao CO, Silva MTT. Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid. Int J Infect Dis. 2020;96:567–9.PubMedPubMedCentralCrossRef
48.
Destras G, Bal A, Escuret V, Morfin F, Lina B, Josset L, Group CO-DHS. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic. Lancet Microbe. 2020;1:e149.PubMedPubMedCentralCrossRef
49.
Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis. 2002;34:1154–7.PubMedCrossRef
50.
Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, Hartman BJ, Kaplan SL, Scheld WM, Whitley RJ, Infectious Diseases Society of A. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47:303–27.PubMedCrossRef
51.
Steiner I, Schmutzhard E, Sellner J, Chaudhuri A, Kennedy PG, European Federation of Neurological S, European Neurologic S. EFNS-ENS guidelines for the use of PCR technology for the diagnosis of infections of the nervous system. Eur J Neurol. 2012;19:1278–91.PubMedCrossRef
52.
53.
Jarius S, Stich O, Rasiah C, Voltz R, Rauer S. Qualitative evidence of Ri specific IgG-synthesis in the cerebrospinal fluid from patients with paraneoplastic neurological syndromes. J Neurol Sci. 2008;268:65–8.PubMedCrossRef
54.
Jarius S, Stich O, Speck J, Rasiah C, Wildemann B, Meinck HM, Rauer S. Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients. J Neuroimmunol 2010;229:219–24.PubMedCrossRef
55.
Stich O, Graus F, Rasiah C, Rauer S. Qualitative evidence of anti-Yo-specific intrathecal antibody synthesis in patients with paraneoplastic cerebellar degeneration. J Neuroimmunol. 2003;141:165–9.PubMedCrossRef
56.
Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig. 1992;70:28–37.PubMedCrossRef
57.
Frederiksen JL, Sindic CJ. Intrathecal synthesis of virus-specific oligoclonal IgG, and of free kappa and free lambda oligoclonal bands in acute monosymptomatic optic neuritis. Comparison with brain MRI. Mult Scler. 1998;4:22–6.PubMedCrossRef
58.
Jarius S, Eichhorn P, Wildemann B, Wick M. Usefulness of antibody index assessment in cerebrospinal fluid from patients negative for total-IgG oligoclonal bands. Fluids Barriers CNS. 2012;9:14.PubMedPubMedCentralCrossRef
59.
Stich O, Kluge J, Speck J, Rauer S. Oligoclonal restriction of antiviral immunoreaction in oligoclonal band-negative MS patients. Acta Neurol Scand. 2015;131:381–8.PubMedCrossRef
60.
Sindic CJ, Monteyne P, Laterre EC. The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis. J Neuroimmunol. 1994;54:75–80.PubMedCrossRef
61.
Brecht I, Weissbrich B, Braun J, Toyka KV, Weishaupt A, Buttmann M. Intrathecal, polyspecific antiviral immune response in oligoclonal band negative multiple sclerosis. PLoS ONE. 2012;7:e40431.PubMedPubMedCentralCrossRef
62.
Stich O, Kluge J, Speck J, Rauer S. Detection of virus-specific (measles, rubella, zoster) oligoclonal IgG-bands in CSF from multiple sclerosis patients without oligoclonal bands of total IgG. Mult Scler. 2009;15:S86.
63.
64.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–8.PubMedPubMedCentralCrossRef
65.
Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17:46–64.PubMedCrossRef
66.
Jin Y, Ji W, Yang H, Chen S, Zhang W, Duan G. Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Signal Transduct Target Ther. 2020;5:293.PubMedPubMedCentralCrossRef
67.
Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther. 2021;27:36–47.PubMedCrossRef
68.
Shi H, Zuo Y, Gandhi AA, Sule G, Yalavarthi S, Gockman K, Madison JA, Wang J, Zuo M, Shi Y, et al. Endothelial cell-activating antibodies in COVID-19. MedRxiv. 2021;109:67.
69.
Yang YH, Huang YH, Chuang YH, Peng CM, Wang LC, Lin YT, Chiang BL. Autoantibodies against human epithelial cells and endothelial cells after severe acute respiratory syndrome (SARS)-associated coronavirus infection. J Med Virol. 2005;77:1–7.PubMedPubMedCentralCrossRef
70.
Buja LM, Wolf DA, Zhao B, Akkanti B, McDonald M, Lelenwa L, Reilly N, Ottaviani G, Elghetany MT, Trujillo DO, et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol. 2020;48:107233.PubMedPubMedCentralCrossRef
71.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383:120–8.PubMedPubMedCentralCrossRef
72.
Lacout C, Rogez J, Orvain C, Nicot C, Rony L, Julien H, Urbanski G. A new diagnosis of systemic capillary leak syndrome in a patient with COVID-19. Rheumatology (Oxford). 2021;60:e19–20.CrossRef
73.
Case R, Ramaniuk A, Martin P, Simpson PJ, Harden C, Ataya A. Systemic capillary leak syndrome secondary to coronavirus disease 2019. Chest. 2020;158:e267–8.PubMedCrossRef
74.
Sussmuth SD, Sperfeld AD, Ludolph AC, Tumani H. Hypercapnia is a possible determinant of the function of the blood-cerebrospinal fluid barrier in amyotrophic lateral sclerosis. Neurochem Res. 2010;35:1071–4.PubMedCrossRef
75.
Pellegrini L, Albecka A, Mallery DL, Kellner MJ, Paul D, Carter AP, James LC, Lancaster MA. SARS-CoV-2 infects the brain choroid plexus and disrupts the blood-CSF barrier in human brain organoids. Cell Stem Cell. 2020;27:951-961.e955.PubMedPubMedCentralCrossRef
76.
77.
Jacob F, Pather SR, Huang WK, Zhang F, Wong SZH, Zhou H, Cubitt B, Fan W, Chen CZ, Xu M, et al. Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-CoV-2 neurotropism predominates in choroid plexus epithelium. Cell Stem Cell. 2020;27:937-950.e939.PubMedPubMedCentralCrossRef
78.
Fishman RA, Sligar K, Hake RB. Effects of leukocytes on brain metabolism in granulocytic brain edema. Ann Neurol. 1977;2:89–94.CrossRef
79.
Jordan GW, Statland B, Halsted C. CSF lactate in diseases of the CNS. Arch Intern Med. 1983;143:85–7.PubMedCrossRef
80.
Kolmel HW, von Maravic M. Correlation of lactic acid level, cell count and cytology in cerebrospinal fluid of patients with bacterial and non-bacterial meningitis. Acta Neurol Scand. 1988;78:6–9.PubMedCrossRef
81.
Andersen NE, Gyring J, Hansen AJ, Laursen H, Siesjo BK. Brain acidosis in experimental pneumococcal meningitis. J Cereb Blood Flow Metab. 1989;9:381–7.PubMedCrossRef
82.
Simchowitz L, Textor JA. Lactic acid secretion by human neutrophils. Evidence for an H+ + lactate- cotransport system. J Gen Physiol. 1992;100:341–67.PubMedCrossRef
83.
Walz W, Mukerji S. Lactate production and release in cultured astrocytes. Neurosci Lett. 1988;86:296–300.PubMedCrossRef
84.
Walz W, Mukerji S. Lactate release from cultured astrocytes and neurons: a comparison. Glia. 1988;1:366–70.PubMedCrossRef
85.
Posner JB, Plum F. Independence of blood and cerebrospinal fluid lactate. Arch Neurol. 1967;16:492–6.PubMedCrossRef
86.
Plum F, Posner JB. Blood and cerebrospinal fluid lactate during hyperventilation. Am J Physiol. 1967;212:864–70.PubMedCrossRef
87.
Hebant B, Miret N, Bouwyn JP, Delafosse E, Lefaucheur R. Absence of pleocytosis in cerebrospinal fluid does not exclude herpes simplex virus encephalitis in elderly adults. J Am Geriatr Soc. 2015;63:1278–9.PubMedCrossRef
88.
Sili U, Kaya A, Mert A, Group HSVES. Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol. 2014;60:112–8.PubMedCrossRef
89.
Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, Franciotta D, Fujihara K, Jacob A, Kim HJ, et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation. 2018;15:134.PubMedPubMedCentralCrossRef
90.
Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.PubMedPubMedCentralCrossRef
91.
Levy M, Wildemann B, Jarius S, Orellano B, Sasidharan S, Weber MS, Stuve O. Immunopathogenesis of neuromyelitis optica. Adv Immunol. 2014;121:213–42.PubMedCrossRef
92.
93.
Jarius S, Hoffmann L, Clover L, Vincent A, Voltz R. CSF findings in patients with voltage gated potassium channel antibody associated limbic encephalitis. J Neurol Sci. 2008;268:74–7.PubMedCrossRef
94.
Guilmot A, Maldonado Slootjes S, Sellimi A, Bronchain M, Hanseeuw B, Belkhir L, Yombi JC, De Greef J, Pothen L, Yildiz H, et al. Immune-mediated neurological syndromes in SARS-CoV-2-infected patients. J Neurol. 2021;268:751–7.PubMedCrossRef
95.
Franke C, Ferse C, Kreye J, Reincke SM, Sanchez-Sendin E, Rocco A, Steinbrenner M, Angermair S, Treskatsch S, Zickler D, et al. High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms. Brain Behav Immun. 2021;93:415–9.PubMedCrossRef
96.
Xu R, Zhou Y, Cai L, Wang L, Han J, Yang X, Chen J, Chen J, Ma C, Shen L. Co-reactivation of the human herpesvirus alpha subfamily (herpes simplex virus-1 and varicella zoster virus) in a critically ill patient with COVID-19. Br J Dermatol. 2020;183:1145–7.PubMedCrossRef
97.
Tartari F, Spadotto A, Zengarini C, Zanoni R, Guglielmo A, Adorno A, Valzania C, Pileri A. Herpes zoster in COVID-19-positive patients. Int J Dermatol. 2020;59:1028–9.PubMedCrossRef
98.
Saati A, Al-Husayni F, Malibari AA, Bogari AA, Alharbi M. Herpes zoster co-infection in an immunocompetent patient with COVID-19. Cureus. 2020;12:e8998.PubMedPubMedCentral
99.
100.
Patel P, Undavia A, Choudry R, Zhang Y, Prabhu AM. COVID-19 associated with concomitant varicella zoster viral encephalitis. Neurol Clin Pract. 2021;11:e219–21.PubMedCrossRefPubMedCentral
Metadata
Title
Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients
Authors
Sven Jarius
Florence Pache
Peter Körtvelyessy
Ilijas Jelčić
Mark Stettner
Diego Franciotta
Emanuela Keller
Bernhard Neumann
Marius Ringelstein
Makbule Senel
Axel Regeniter
Rea Kalantzis
Jan F. Willms
Achim Berthele
Markus Busch
Marco Capobianco
Amanda Eisele
Ina Reichen
Rick Dersch
Sebastian Rauer
Katharina Sandner
Ilya Ayzenberg
Catharina C. Gross
Harald Hegen
Michael Khalil
Ingo Kleiter
Thorsten Lenhard
Jürgen Haas
Orhan Aktas
Klemens Angstwurm
Christoph Kleinschnitz
Jan Lewerenz
Hayrettin Tumani
Friedemann Paul
Martin Stangel
Klemens Ruprecht
Brigitte Wildemann
in cooperation with the German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-021-02339-0

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