Tissue factor upregulation is associated with SARS-CoV-2 in the lungs of COVID-19 patients.
COVID-19
SARS-CoV-2
fibrin
thrombosis
tissue factor
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
02
07
2021
received:
22
12
2020
accepted:
06
07
2021
pubmed:
9
7
2021
medline:
1
9
2021
entrez:
8
7
2021
Statut:
ppublish
Résumé
A substantial proportion of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe/critical coronavirus disease 2019 (COVID-19) characterized by acute respiratory distress syndrome (ARDS) with thrombosis. We tested the hypothesis that SARS-CoV-2--induced upregulation of tissue factor (TF) expression may be responsible for thrombus formation in COVID-19. We compared autopsy lung tissues from 11 patients with COVID-19--associated ARDS with samples from 6 patients with ARDS from other causes (non-COVID-19 ARDS) and 11 normal control lungs. Dual RNA in situ hybridization for SARS-CoV-2 and TF identified sporadic clustered SARS-CoV-2 with prominent co-localization of SARS-CoV-2 and TF RNA. TF expression was 2-fold higher in COVID-19 than in non-COVID-19 ARDS lungs (P = .017) and correlated with the intensity of SARS-CoV-2 staining (R These data suggest that upregulation of TF expression is associated with thrombus formation in COVID-19 lungs and could be a key therapeutic target. Correlation of TF expression with SARS-CoV-2 in lungs of COVID-19 patients also raises the possibility of direct TF induction by the virus.
Sections du résumé
BACKGROUND
A substantial proportion of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe/critical coronavirus disease 2019 (COVID-19) characterized by acute respiratory distress syndrome (ARDS) with thrombosis.
OBJECTIVES
We tested the hypothesis that SARS-CoV-2--induced upregulation of tissue factor (TF) expression may be responsible for thrombus formation in COVID-19.
METHODS
We compared autopsy lung tissues from 11 patients with COVID-19--associated ARDS with samples from 6 patients with ARDS from other causes (non-COVID-19 ARDS) and 11 normal control lungs.
RESULTS
Dual RNA in situ hybridization for SARS-CoV-2 and TF identified sporadic clustered SARS-CoV-2 with prominent co-localization of SARS-CoV-2 and TF RNA. TF expression was 2-fold higher in COVID-19 than in non-COVID-19 ARDS lungs (P = .017) and correlated with the intensity of SARS-CoV-2 staining (R
CONCLUSIONS
These data suggest that upregulation of TF expression is associated with thrombus formation in COVID-19 lungs and could be a key therapeutic target. Correlation of TF expression with SARS-CoV-2 in lungs of COVID-19 patients also raises the possibility of direct TF induction by the virus.
Identifiants
pubmed: 34236752
doi: 10.1111/jth.15451
pmc: PMC8565501
mid: NIHMS1751126
pii: S1538-7836(22)01901-8
doi:
Substances chimiques
Thromboplastin
9035-58-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2268-2274Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103639
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM114731
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM103639
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148123
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL148123
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM114731
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123605
Pays : United States
Organisme : NHLBI NIH HHS
ID : HL123605
Pays : United States
Informations de copyright
© 2021 International Society on Thrombosis and Haemostasis.
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