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Infection of Brain ...
Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.
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- Bocci, Matteo (author)
- Lund 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
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- Oudenaarden, Clara (author)
- Lund 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
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- Sàenz-Sardà, Xavier (author)
- Lund University,Skåne University Hospital
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- Simrén, Joel, 1996 (author)
- Gothenburg 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
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- Edén, Arvid, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska Academy,Sahlgrenska University Hospital
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- Sjölund, Jonas (author)
- Lund 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
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- Möller, Christina (author)
- Lund University,Lunds universitet,Allmänmedicin och samhällsmedicin,Forskargrupper vid Lunds universitet,Family Medicine and Community Medicine,Lund University Research Groups
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- Gisslén, Magnus, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg 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
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- Englund, Elisabet (author)
- Lund 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
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- Pietras, Kristian (author)
- Lund 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
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(creator_code:org_t)
- 2021-10-27
- 2021
- English.
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:21
- Related links:
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
Subject headings
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Angiotensin-Converting Enzyme 2
- genetics
- metabolism
- Animals
- Blood-Brain Barrier
- Brain
- pathology
- virology
- COVID-19
- etiology
- physiopathology
- Case-Control Studies
- Encephalitis
- Viral
- pathology
- virology
- Fibrinogen
- metabolism
- Humans
- Immunohistochemistry
- methods
- Mice
- Pericytes
- metabolism
- pathology
- virology
- Receptor
- Platelet-Derived Growth Factor beta
- cerebrospinal fluid
- ACE2
- Blood–brain barrier
- COVID‐19
- Infection
- Multiplexed IHC
- SARS‐CoV‐2
- Vasculature
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Bocci, Matteo
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Oudenaarden, Cla ...
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Sàenz-Sardà, Xav ...
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Simrén, Joel, 19 ...
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Edén, Arvid, 197 ...
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Sjölund, Jonas
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Möller, Christin ...
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Gisslén, Magnus, ...
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Zetterberg, Henr ...
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Englund, Elisabe ...
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Pietras, Kristia ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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International jo ...
- By the university
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University of Gothenburg
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Lund University