tetano
Editor, Senior Moderator
J Thromb Haemost
. 2021 Jul 8.
doi: 10.1111/jth.15451. Online ahead of print.
Tissue Factor upregulation is associated with SARS-CoV-2 in the lungs of COVID-19 patients
Sandeep Subrahmanian[SUP] 1 [/SUP], Alain Borczuk[SUP] 2 [/SUP], Steven Salvatore[SUP] 2 [/SUP], Kar-Ming Fung[SUP] 3 [/SUP], Joan T Merrill[SUP] 4 [/SUP], Jeffrey Laurence[SUP] 5 [/SUP], Jasimuddin Ahamed[SUP] 1 3 6 [/SUP]
Affiliations
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 eleven patients with COVID-19-associated ARDS with samples from six patients with ARDS from other causes (non-COVID-19 ARDS) and eleven 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=0.017) and correlated with the intensity of SARS-CoV-2 staining (R[SUP]2[/SUP] =0.36, p=0.04). By immunofluorescence, TF protein expression was 2.1-fold higher in COVID-19 vs. non-COVID-19 ARDS lungs (p=0.0048) and 11-fold (p<0.001) higher than control lungs. Fibrin thrombi and thrombi positive for platelet factor 4 were found in close proximity to regions expressing TF in COVID-19 ARDS lung, and correlated with TF expression (fibrin, R[SUP]2[/SUP] =0.52, p<0.001; PF4, R[SUP]2[/SUP] =0.59, p<0.001).
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 also raises the possibility of direct TF induction by the virus.
Keywords: COVID-19; Fibrin; SARS-CoV-2; Thrombosis; Tissue Factor.
. 2021 Jul 8.
doi: 10.1111/jth.15451. Online ahead of print.
Tissue Factor upregulation is associated with SARS-CoV-2 in the lungs of COVID-19 patients
Sandeep Subrahmanian[SUP] 1 [/SUP], Alain Borczuk[SUP] 2 [/SUP], Steven Salvatore[SUP] 2 [/SUP], Kar-Ming Fung[SUP] 3 [/SUP], Joan T Merrill[SUP] 4 [/SUP], Jeffrey Laurence[SUP] 5 [/SUP], Jasimuddin Ahamed[SUP] 1 3 6 [/SUP]
Affiliations
- PMID: 34236752
- DOI: 10.1111/jth.15451
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 eleven patients with COVID-19-associated ARDS with samples from six patients with ARDS from other causes (non-COVID-19 ARDS) and eleven 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=0.017) and correlated with the intensity of SARS-CoV-2 staining (R[SUP]2[/SUP] =0.36, p=0.04). By immunofluorescence, TF protein expression was 2.1-fold higher in COVID-19 vs. non-COVID-19 ARDS lungs (p=0.0048) and 11-fold (p<0.001) higher than control lungs. Fibrin thrombi and thrombi positive for platelet factor 4 were found in close proximity to regions expressing TF in COVID-19 ARDS lung, and correlated with TF expression (fibrin, R[SUP]2[/SUP] =0.52, p<0.001; PF4, R[SUP]2[/SUP] =0.59, p<0.001).
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 also raises the possibility of direct TF induction by the virus.
Keywords: COVID-19; Fibrin; SARS-CoV-2; Thrombosis; Tissue Factor.