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March 2021; 8 (2) Clinical/Scientific NotesOpen Access

Presence of SARS-CoV-2 Transcripts in the Choroid Plexus of MS and Non-MS Patients With COVID-19

View ORCID ProfileVidmante Fuchs, View ORCID ProfileMichael Kutza, View ORCID ProfileSven Wischnewski, View ORCID ProfileNikolaus Deigendesch, Luc Lutz, Laila Kulsvehagen, Gerda Ricken, Ludwig Kappos, View ORCID ProfileAlexandar Tzankov, Simon Hametner, Stephan Frank, View ORCID ProfileLucas Schirmer, View ORCID ProfileAnne-Katrin Pröbstel
First published January 27, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000957
Vidmante Fuchs
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Vidmante Fuchs
  • For correspondence: vidmante.fuchs@unibas.ch
Michael Kutza
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Michael Kutza
  • For correspondence: vidmante.fuchs@unibas.ch
Sven Wischnewski
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Sven Wischnewski
  • For correspondence: s.wischnewski@stud.uni-heidelberg.de
Nikolaus Deigendesch
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Nikolaus Deigendesch
  • For correspondence: nikolaus.deigendesch@usb.ch
Luc Lutz
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: luc.lutz@unibas.ch
Laila Kulsvehagen
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: laila.kulsvehagen@unibas.ch
Gerda Ricken
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: gerda.ricken@meduniwien.ac.at
Ludwig Kappos
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: ludwig.kappos@usb.ch
Alexandar Tzankov
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Alexandar Tzankov
  • For correspondence: alexandar.tzankov@usb.ch
Simon Hametner
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: simon.hametner@meduniwien.ac.at
Stephan Frank
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • For correspondence: stephan.frank@usb.ch
Lucas Schirmer
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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  • ORCID record for Lucas Schirmer
  • For correspondence: lucas.schirmer@medma.uni-heidelberg.de
Anne-Katrin Pröbstel
From the Multiple Sclerosis Center (V.F., L.L., L. Kulsvehagen, L. Kappos), Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine, University Hospital and University of Basel, Switzerland; Department of Neurology (M.K., S.W., L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; Pathology (N.D., A.T., S.F.), Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (G.R., S.H.), Division of Neuropathology and Neurochemistry, Medical University Vienna, Austria; Mannheim Center for Translational Neuroscience and Institute for Innate Immunoscience (L.S.), Medical Faculty Mannheim, Heidelberg University, Germany; and Interdisciplinary Center for Neurosciences (L.S.), Heidelberg University, Germany.
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Citation
Presence of SARS-CoV-2 Transcripts in the Choroid Plexus of MS and Non-MS Patients With COVID-19
Vidmante Fuchs, Michael Kutza, Sven Wischnewski, Nikolaus Deigendesch, Luc Lutz, Laila Kulsvehagen, Gerda Ricken, Ludwig Kappos, Alexandar Tzankov, Simon Hametner, Stephan Frank, Lucas Schirmer, Anne-Katrin Pröbstel
Neurol Neuroimmunol Neuroinflamm Mar 2021, 8 (2) e957; DOI: 10.1212/NXI.0000000000000957

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    Figure 1 Histopathologic Assessment of MS COVID-19 Brain

    (A–B) Macroscopically visible lesions were assessed by (A) H&E, LFB staining, and MBP, Iba1, CD45, and (B) dysferlin immunohistochemical evaluation. Given the lack of ongoing myelin phagocytosis presence of Iba1+ macrophages, all examined lesions were staged as chronic-inactive. Scale bar indicates 100 μm. (C) Assessing the presence and spatial distribution of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) transcripts by in situ hybridization in MS COVID-19 compared with non-COVID-19 tissue, we found presence of SARS-CoV-2 transcripts (pink arrows) in lung tissue, ependymal cells, and choroid plexus (CP) epithelial cells from MS-COVID-19 in comparable amount with non-MS COVID-19 CP epithelial cells with some coexpression of ACE2 (white arrows). Notably, SARS-CoV-2 transcripts were not present in MS lesions areas, suggesting CP epithelial cells as a key constraint of viral CNS entry. Arrows indicate positive cells. Left and right panel show different areas of the respective tissue section. Scale bar indicates 20 μm. COVID-19 = coronavirus disease 2019; H&E = hematoxylin and eosin; LFE = luxol fast blue; MBP = myelin basic protein; PV = periventricular; WM = white matter.

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