Infection of brain pericytes underlying neuropathology of covid‐19 patients

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number11622
JournalInternational Journal of Molecular Sciences
Issue number21
Publication statusPublished - 2021 Nov 1

Subject classification (UKÄ)

  • Neurology
  • Infectious Medicine

Free keywords

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


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