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@ARTICLE{Rong:273942,
      author       = {Rong, Zhouyi and Mai, Hongcheng and Ebert, Gregor and
                      Kapoor, Saketh and Puelles, Victor G and Czogalla, Jan and
                      Hu, Senbin and Su, Jinpeng and Prtvar, Danilo and Singh,
                      Inderjeet and Schädler, Julia and Delbridge, Claire and
                      Steinke, Hanno and Frenzel, Hannah and Schmidt, Katja and
                      Braun, Christian and Bruch, Gina and Ruf, Viktoria and Ali,
                      Mayar and Sühs, Kurt-Wolfram and Nemati, Mojtaba and
                      Hopfner, Franziska and Ulukaya, Selin and Jeridi, Denise and
                      Mistretta, Daniele and Caliskan, Özüm Sehnaz and
                      Wettengel, Jochen Martin and Cherif, Fatma and Kolabas,
                      Zeynep Ilgin and Molbay, Müge and Horvath, Izabela and
                      Zhao, Shan and Krahmer, Natalie and Yildirim, Ali Önder and
                      Ussar, Siegfried and Herms, Jochen and Huber, Tobias B and
                      Tahirovic, Sabina and Schwarzmaier, Susanne M and Plesnila,
                      Nikolaus and Höglinger, Günter and Ondruschka, Benjamin
                      and Bechmann, Ingo and Protzer, Ulrike and Elsner, Markus
                      and Bhatia, Harsharan Singh and Hellal, Farida and Ertürk,
                      Ali},
      title        = {{P}ersistence of spike protein at the skull-meninges-brain
                      axis may contribute to the neurological sequelae of
                      {COVID}-19.},
      journal      = {Cell host and microbe},
      volume       = {32},
      number       = {12},
      issn         = {1931-3128},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2024-01416},
      pages        = {2112 - 2130.e10},
      year         = {2024},
      abstract     = {SARS-CoV-2 infection is associated with long-lasting
                      neurological symptoms, although the underlying mechanisms
                      remain unclear. Using optical clearing and imaging, we
                      observed the accumulation of SARS-CoV-2 spike protein in the
                      skull-meninges-brain axis of human COVID-19 patients,
                      persisting long after viral clearance. Further, biomarkers
                      of neurodegeneration were elevated in the cerebrospinal
                      fluid from long COVID patients, and proteomic analysis of
                      human skull, meninges, and brain samples revealed
                      dysregulated inflammatory pathways and
                      neurodegeneration-associated changes. Similar distribution
                      patterns of the spike protein were observed in
                      SARS-CoV-2-infected mice. Injection of spike protein alone
                      was sufficient to induce neuroinflammation, proteome changes
                      in the skull-meninges-brain axis, anxiety-like behavior, and
                      exacerbated outcomes in mouse models of stroke and traumatic
                      brain injury. Vaccination reduced but did not eliminate
                      spike protein accumulation after infection in mice. Our
                      findings suggest persistent spike protein at the brain
                      borders may contribute to lasting neurological sequelae of
                      COVID-19.},
      keywords     = {COVID-19: metabolism / COVID-19: virology / Animals / Spike
                      Glycoprotein, Coronavirus: metabolism / Humans / Mice /
                      SARS-CoV-2 / Brain: virology / Brain: metabolism / Disease
                      Models, Animal / Meninges: virology / Meninges: metabolism /
                      Skull: virology / Male / Female / Proteomics / Stroke:
                      metabolism / Stroke: virology / Neuroinflammatory Diseases:
                      metabolism / Neuroinflammatory Diseases: virology / Mice,
                      Inbred C57BL / Brain Injuries, Traumatic: metabolism / Brain
                      Injuries, Traumatic: virology / SARS-CoV-2 (Other) / brain
                      (Other) / long COVID (Other) / mRNA vaccine (Other) /
                      meninges (Other) / neurodegeneration (Other) /
                      neuroinflammation (Other) / skull (Other) / spike protein
                      (Other) / tissue clearing (Other) / Spike Glycoprotein,
                      Coronavirus (NLM Chemicals) / spike protein, SARS-CoV-2 (NLM
                      Chemicals)},
      cin          = {AG Tahirovic / Clinical Research (Munich)},
      ddc          = {570},
      cid          = {I:(DE-2719)1140003 / I:(DE-2719)1111015},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39615487},
      doi          = {10.1016/j.chom.2024.11.007},
      url          = {https://pub.dzne.de/record/273942},
}