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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Infection of brain pericytes underlying neuropathology of covid‐19 patients

Author

  • Matteo Bocci
  • Clara Oudenaarden
  • Xavier Sàenz‐sardà
  • Joel Simrén
  • Arvid Edén
  • Jonas Sjölund
  • Christina Möller
  • Magnus Gisslén
  • Henrik Zetterberg
  • Elisabet Englund
  • Kristian Pietras
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Summary, in English

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 sympto-matology 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 neuro-vascular 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 macro-phage 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.

Department/s

  • Experimental oncology
  • Division of Translational Cancer Research
  • Family Medicine and Community Medicine
  • Pathology, Lund
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2021-11-01

Language

English

Publication/Series

International Journal of Molecular Sciences

Volume

22

Issue

21

Document type

Journal article

Publisher

MDPI AG

Topic

  • Neurology
  • Infectious Medicine

Keywords

  • ACE2
  • Blood–brain barrier
  • Brain
  • COVID‐19
  • Infection
  • Multiplexed IHC
  • Pericytes
  • SARS‐CoV‐2
  • Vasculature

Status

Published

Research group

  • Experimental oncology
  • Family Medicine and Community Medicine

ISBN/ISSN/Other

  • ISSN: 1661-6596