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

Bocci M, Oudenaarden C, Sàenz-Sardà X, Simrén J, Edén A, Sjölund J, Möller C, Gisslén M, Zetterberg H, Englund E, Pietras K

Int J Mol Sci 22 (21) 11622 [2021-10-27; online 2021-10-27]

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.

Category: Health

Funder: H2020

Funder: KAW/SciLifeLab

Funder: VR

Research Area: Biobanks for COVID-19 research

Type: Journal article

PubMed 34769052

DOI 10.3390/ijms222111622

Crossref 10.3390/ijms222111622

pmc: PMC8583965
pii: ijms222111622

Publications 9.5.0