Tissue factor upregulation is associated with SARS-CoV-2 in the lungs of COVID-19 patients.

TitleTissue factor upregulation is associated with SARS-CoV-2 in the lungs of COVID-19 patients.
Publication TypeJournal Article
Year of Publication2021
AuthorsSubrahmanian S, Borczuk A, Salvatore S, Fung K-M, Merrill JT, Laurence J, Ahamed J
JournalJ Thromb Haemost
Volume19
Issue9
Pagination2268-2274
Date Published2021 09
ISSN1538-7836
KeywordsCOVID-19, Humans, Lung, SARS-CoV-2, Thromboplastin, Up-Regulation
Abstract

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  = .36, P = .04). By immunofluorescence, TF protein expression was 2.1-fold higher in COVID-19 versus non-COVID-19 ARDS lungs (P = .0048) and 11-fold (P < .001) higher than control lungs. Fibrin thrombi and thrombi positive for platelet factor 4 (PF4) were found in close proximity to regions expressing TF in COVID-19 ARDS lung, and correlated with TF expression (fibrin, R  = .52, P < .001; PF4, R  = .59, P < .001).

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.

DOI10.1111/jth.15451
Alternate JournalJ Thromb Haemost
PubMed ID34236752
Grant ListGM103639 / GM / NIGMS NIH HHS / United States
GM114731 / GM / NIGMS NIH HHS / United States
HL123605 / HL / NHLBI NIH HHS / United States
HL148123 / HL / NHLBI NIH HHS / United States
GM103639 / GM / NIGMS NIH HHS / United States
GM114731 / GM / NIGMS NIH HHS / United States
HL123605 / HL / NHLBI NIH HHS / United States
HL148123 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Steven P. Salvatore, M.D.

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