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024 7 _ |a 10.1016/S1474-4422(20)30308-2
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024 7 _ |a 1474-4422
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037 _ _ |a DZNE-2021-00059
082 _ _ |a 610
100 1 _ |a Matschke, Jakob
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245 _ _ |a Neuropathology of patients with COVID-19 in Germany: a post-mortem case series
260 _ _ |a London
|c 2020
|b Lancet Publ. Group
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520 _ _ |a 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).
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650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Autopsy: methods
|2 MeSH
650 _ 2 |a Betacoronavirus: isolation & purification
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain: virology
|2 MeSH
650 _ 2 |a COVID-19
|2 MeSH
650 _ 2 |a Coronavirus Infections: epidemiology
|2 MeSH
650 _ 2 |a Coronavirus Infections: genetics
|2 MeSH
650 _ 2 |a Coronavirus Infections: pathology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Germany: epidemiology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Neuropathology
|2 MeSH
650 _ 2 |a Pandemics
|2 MeSH
650 _ 2 |a Pneumonia, Viral: epidemiology
|2 MeSH
650 _ 2 |a Pneumonia, Viral: genetics
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650 _ 2 |a Pneumonia, Viral: pathology
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650 _ 2 |a SARS-CoV-2
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650 _ 2 |a Transcriptome: genetics
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700 1 _ |a Lütgehetmann, Marc
|b 1
700 1 _ |a Hagel, Christian
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700 1 _ |a Sperhake, Jan P
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700 1 _ |a Schröder, Ann Sophie
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700 1 _ |a Edler, Carolin
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700 1 _ |a Mushumba, Herbert
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700 1 _ |a Fitzek, Antonia
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700 1 _ |a Allweiss, Lena
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700 1 _ |a Dandri, Maura
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700 1 _ |a Dottermusch, Matthias
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700 1 _ |a Heinemann, Axel
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700 1 _ |a Pfefferle, Susanne
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700 1 _ |a Schwabenland, Marius
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700 1 _ |a Sumner Magruder, Daniel
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700 1 _ |a Bonn, Stefan
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700 1 _ |a Prinz, Marco
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700 1 _ |a Gerloff, Christian
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700 1 _ |a Püschel, Klaus
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700 1 _ |a Krasemann, Susanne
|b 19
700 1 _ |a Aepfelbacher, Martin
|b 20
700 1 _ |a Glatzel, Markus
|b 21
773 _ _ |a 10.1016/S1474-4422(20)30308-2
|g Vol. 19, no. 11, p. 919 - 929
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|t The lancet / Neurology
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|y 2020
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