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@ARTICLE{Matschke:154197,
      author       = {Matschke, Jakob and Lütgehetmann, Marc and Hagel,
                      Christian and Sperhake, Jan P and Schröder, Ann Sophie and
                      Edler, Carolin and Mushumba, Herbert and Fitzek, Antonia and
                      Allweiss, Lena and Dandri, Maura and Dottermusch, Matthias
                      and Heinemann, Axel and Pfefferle, Susanne and Schwabenland,
                      Marius and Sumner Magruder, Daniel and Bonn, Stefan and
                      Prinz, Marco and Gerloff, Christian and Püschel, Klaus and
                      Krasemann, Susanne and Aepfelbacher, Martin and Glatzel,
                      Markus},
      title        = {{N}europathology of patients with {COVID}-19 in {G}ermany:
                      a post-mortem case series},
      journal      = {The lancet / Neurology},
      volume       = {19},
      number       = {11},
      issn         = {1474-4422},
      address      = {London},
      publisher    = {Lancet Publ. Group},
      reportid     = {DZNE-2021-00059},
      pages        = {919 - 929},
      year         = {2020},
      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).},
      keywords     = {Aged / Aged, 80 and over / Autopsy: methods /
                      Betacoronavirus: isolation $\&$ purification / Brain:
                      pathology / Brain: virology / COVID-19 / Coronavirus
                      Infections: epidemiology / Coronavirus Infections: genetics
                      / Coronavirus Infections: pathology / Female / Germany:
                      epidemiology / Humans / Male / Middle Aged / Neuropathology
                      / Pandemics / Pneumonia, Viral: epidemiology / Pneumonia,
                      Viral: genetics / Pneumonia, Viral: pathology / SARS-CoV-2 /
                      Transcriptome: genetics},
      cin          = {AG Bonn 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1410003},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC7535629},
      pubmed       = {pmid:33031735},
      doi          = {10.1016/S1474-4422(20)30308-2},
      url          = {https://pub.dzne.de/record/154197},
}