Journal Article

DZNE-2021-00059

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuropathology of patients with COVID-19 in Germany: a post-mortem case series

Matschke, J. ; Lütgehetmann, M. ; Hagel, C. ; Sperhake, J. P. ; Schröder, A. S. ; Edler, C. ; Mushumba, H. ; Fitzek, A. ; Allweiss, L. ; Dandri, M. ; Dottermusch, M. ; Heinemann, A. ; Pfefferle, S. ; Schwabenland, M. ; Sumner Magruder, D. ; Bonn, S.DZNE* ; Prinz, M. ; Gerloff, C. ; Püschel, K. ; Krasemann, S. ; Aepfelbacher, M. ; Glatzel, M.

2020
Lancet Publ. Group London

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Please use a persistent id in citations: doi:10.1016/S1474-4422(20)30308-2

Abstract: Background: Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS.Methods: In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions.Findings: 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes.Interpretation: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.Funding: German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Autopsy: methods (MeSH) ; Betacoronavirus: isolation & purification (MeSH) ; Brain: pathology (MeSH) ; Brain: virology (MeSH) ; COVID-19 (MeSH) ; Coronavirus Infections: epidemiology (MeSH) ; Coronavirus Infections: genetics (MeSH) ; Coronavirus Infections: pathology (MeSH) ; Female (MeSH) ; Germany: epidemiology (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Neuropathology (MeSH) ; Pandemics (MeSH) ; Pneumonia, Viral: epidemiology (MeSH) ; Pneumonia, Viral: genetics (MeSH) ; Pneumonia, Viral: pathology (MeSH) ; SARS-CoV-2 (MeSH) ; Transcriptome: genetics (MeSH)

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Contributing Institute(s):

1. Computational analysis of biological networks (AG Bonn 1)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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