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  • Bocci, MatteoLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups (author)

Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-10-27
  • MDPI AG,2021

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/310847
  • https://gup.ub.gu.se/publication/310847URI
  • https://doi.org/10.3390/ijms222111622DOI
  • https://lup.lub.lu.se/record/fec75098-c902-49b4-821a-17dcfb51263dURI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood-brain barrier.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Oudenaarden, ClaraLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups(Swepub:lu)med-cod (author)
  • Sàenz-Sardà, XavierLund University,Skåne University Hospital (author)
  • Simrén, Joel,1996Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy(Swepub:gu)xsimrj (author)
  • Edén, Arvid,1975Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska Academy,Sahlgrenska University Hospital(Swepub:gu)xedear (author)
  • Sjölund, JonasLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups(Swepub:lu)molm-sjo (author)
  • Möller, ChristinaLund University,Lunds universitet,Allmänmedicin och samhällsmedicin,Forskargrupper vid Lunds universitet,Family Medicine and Community Medicine,Lund University Research Groups(Swepub:lu)ch4701mo (author)
  • Gisslén, Magnus,1962Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska University Hospital,Sahlgrenska Academy(Swepub:gu)xgissm (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital,University College London(Swepub:lu)med-hiz (author)
  • Englund, ElisabetLund University,Lunds universitet,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-een (author)
  • Pietras, KristianLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups(Swepub:lu)med-kpi (author)
  • Avdelningen för translationell cancerforskningInstitutionen för laboratoriemedicin (creator_code:org_t)

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  • In:International journal of molecular sciences: MDPI AG22:211422-00671661-6596

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