Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein.
Adult
Aged
Aged, 80 and over
Animals
Autopsy
/ methods
COVID-19
/ virology
Disease Models, Animal
Endothelial Cells
/ metabolism
Female
Humans
Male
Mice
Microvessels
/ metabolism
Middle Aged
Protein Subunits
/ metabolism
RNA, Viral
/ genetics
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
COVID-19
S1 subunit
SARS-CoV-2
Spike protein
Journal
Annals of diagnostic pathology
ISSN: 1532-8198
Titre abrégé: Ann Diagn Pathol
Pays: United States
ID NLM: 9800503
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
17
11
2020
accepted:
16
12
2020
pubmed:
29
12
2020
medline:
18
3
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.
Identifiants
pubmed: 33360731
pii: S1092-9134(20)30228-8
doi: 10.1016/j.anndiagpath.2020.151682
pmc: PMC7758180
pii:
doi:
Substances chimiques
Protein Subunits
0
RNA, Viral
0
Spike Glycoprotein, Coronavirus
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
151682Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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