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000154197 005__ 20240618100829.0
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000154197 0247_ $$2ISSN$$a1474-4465
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000154197 037__ $$aDZNE-2021-00059
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000154197 1001_ $$aMatschke, Jakob$$b0
000154197 245__ $$aNeuropathology of patients with COVID-19 in Germany: a post-mortem case series
000154197 260__ $$aLondon$$bLancet Publ. Group$$c2020
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000154197 520__ $$aBackground: 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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000154197 650_2 $$2MeSH$$aAged
000154197 650_2 $$2MeSH$$aAged, 80 and over
000154197 650_2 $$2MeSH$$aAutopsy: methods
000154197 650_2 $$2MeSH$$aBetacoronavirus: isolation & purification
000154197 650_2 $$2MeSH$$aBrain: pathology
000154197 650_2 $$2MeSH$$aBrain: virology
000154197 650_2 $$2MeSH$$aCOVID-19
000154197 650_2 $$2MeSH$$aCoronavirus Infections: epidemiology
000154197 650_2 $$2MeSH$$aCoronavirus Infections: genetics
000154197 650_2 $$2MeSH$$aCoronavirus Infections: pathology
000154197 650_2 $$2MeSH$$aFemale
000154197 650_2 $$2MeSH$$aGermany: epidemiology
000154197 650_2 $$2MeSH$$aHumans
000154197 650_2 $$2MeSH$$aMale
000154197 650_2 $$2MeSH$$aMiddle Aged
000154197 650_2 $$2MeSH$$aNeuropathology
000154197 650_2 $$2MeSH$$aPandemics
000154197 650_2 $$2MeSH$$aPneumonia, Viral: epidemiology
000154197 650_2 $$2MeSH$$aPneumonia, Viral: genetics
000154197 650_2 $$2MeSH$$aPneumonia, Viral: pathology
000154197 650_2 $$2MeSH$$aSARS-CoV-2
000154197 650_2 $$2MeSH$$aTranscriptome: genetics
000154197 7001_ $$aLütgehetmann, Marc$$b1
000154197 7001_ $$aHagel, Christian$$b2
000154197 7001_ $$aSperhake, Jan P$$b3
000154197 7001_ $$0P:(DE-HGF)0$$aSchröder, Ann Sophie$$b4
000154197 7001_ $$aEdler, Carolin$$b5
000154197 7001_ $$aMushumba, Herbert$$b6
000154197 7001_ $$aFitzek, Antonia$$b7
000154197 7001_ $$aAllweiss, Lena$$b8
000154197 7001_ $$aDandri, Maura$$b9
000154197 7001_ $$aDottermusch, Matthias$$b10
000154197 7001_ $$aHeinemann, Axel$$b11
000154197 7001_ $$aPfefferle, Susanne$$b12
000154197 7001_ $$aSchwabenland, Marius$$b13
000154197 7001_ $$aSumner Magruder, Daniel$$b14
000154197 7001_ $$0P:(DE-2719)2810547$$aBonn, Stefan$$b15$$udzne
000154197 7001_ $$aPrinz, Marco$$b16
000154197 7001_ $$aGerloff, Christian$$b17
000154197 7001_ $$aPüschel, Klaus$$b18
000154197 7001_ $$aKrasemann, Susanne$$b19
000154197 7001_ $$aAepfelbacher, Martin$$b20
000154197 7001_ $$aGlatzel, Markus$$b21
000154197 773__ $$0PERI:(DE-600)2079704-7$$a10.1016/S1474-4422(20)30308-2$$gVol. 19, no. 11, p. 919 - 929$$n11$$p919 - 929$$tThe lancet <London> / Neurology$$v19$$x1474-4422$$y2020
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