Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.
Aged, 80 and over
Animals
Bronchoalveolar Lavage
C-Reactive Protein
/ analysis
COVID-19
/ blood
Complement Activation
Cytokines
/ blood
Female
Humans
Inflammation
/ blood
Lung
/ pathology
Macaca mulatta
Macrophages
/ immunology
Male
Platelet Activation
SARS-CoV-2
/ genetics
Thrombosis
/ blood
Transcriptome
Vascular Diseases
/ blood
IFNα
SARS-CoV-2
coagulation
collagen
complement
macrophage
platelet
thrombosis
vWF
vascular
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 11 2020
25 11 2020
Historique:
received:
27
08
2020
revised:
30
09
2020
accepted:
05
10
2020
pubmed:
17
10
2020
medline:
15
12
2020
entrez:
16
10
2020
Statut:
ppublish
Résumé
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.
Identifiants
pubmed: 33065030
pii: S0092-8674(20)31311-8
doi: 10.1016/j.cell.2020.10.005
pmc: PMC7546181
pii:
doi:
Substances chimiques
Cytokines
0
C-Reactive Protein
9007-41-4
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1354-1366.e13Subventions
Organisme : NCI NIH HHS
ID : U54 CA225088
Pays : United States
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA260476
Pays : United States
Organisme : NIH HHS
ID : S10 OD025002
Pays : United States
Organisme : NIH HHS
ID : S10 OD026799
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI135098
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128751
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI129797
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI149670
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126603
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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