Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5
Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:3b745cc794fd43db9f5982030c9086d22021-11-11T09:18:10ZPlatelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A52297-055X10.3389/fcvm.2021.779073https://doaj.org/article/3b745cc794fd43db9f5982030c9086d22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.779073/fullhttps://doaj.org/toc/2297-055XBackground: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional and biochemical profile in patients with COVID-19 in dependence of mortality within 5-days after hospitalization.Methods: The COVID-19-related platelet phenotype was examined by analyzing their basal activation state via integrin αIIbβ3 activation using flow cytometry and the proteome by unbiased two-dimensional differential in-gel fluorescence electrophoresis. In total we monitored 98 surviving and 12 non-surviving COVID-19 patients over 5 days of hospital stay and compared them to healthy controls (n = 12).Results: Over the observation period the level of basal αIIbβ3 activation on platelets from non-surviving COVID-19 patients decreased compared to survivors. In line with this finding, proteomic analysis revealed a decrease in the total amount of integrin αIIb (ITGA2B), a subunit of αIIbβ3, in COVID-19 patients compared to healthy controls; the decline was even more pronounced for the non-survivors. Consumption of the fibrin-stabilizing factor coagulation factor XIIIA (F13A1) was higher in platelets from COVID-19 patients and tended to be higher in non-survivors; plasma concentrations of the latter also differed significantly. Depending on COVID-19 disease status and mortality, increased amounts of annexin A5 (ANXA5), eukaryotic initiation factor 4A-I (EIF4A1), and transaldolase (TALDO1) were found in the platelet proteome and also correlated with the nasopharyngeal viral load. Dysregulation of these proteins may play a role for virus replication. ANXA5 has also been identified as an autoantigen of the antiphospholipid syndrome, which is common in COVID-19 patients. Finally, the levels of two different protein disulfide isomerases, P4HB and PDIA6, which support thrombosis, were increased in the platelets of COVID-19 patients.Conclusion: Platelets from COVID-19 patients showed significant changes in the activation phenotype, in the processing of the final coagulation factor F13A1 and the phospholipid-binding protein ANXA5 compared to healthy subjects. Additionally, these results demonstrate specific alterations in platelets during COVID-19, which are significantly linked to fatal outcome.Huriye ErcanWaltraud Cornelia SchrottmaierAnita PirabeAnna SchmuckenschlagerDavid PereyraDavid PereyraJonas SantolJonas SantolErich PawelkaMarianna T. TraugottChristian SchörgenhoferTamara SeitzMario KarolyiJae-Won YangBernd JilmaAlexander ZoufalyAlice AssingerMaria ZellnerFrontiers Media S.A.articleCOVID-19thrombosisplateletsintegrin αIIbβ3coagulation factor XIII (FXIII, F13A1)antiphospholipid syndromeDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021) |
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COVID-19 thrombosis platelets integrin αIIbβ3 coagulation factor XIII (FXIII, F13A1) antiphospholipid syndrome Diseases of the circulatory (Cardiovascular) system RC666-701 |
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COVID-19 thrombosis platelets integrin αIIbβ3 coagulation factor XIII (FXIII, F13A1) antiphospholipid syndrome Diseases of the circulatory (Cardiovascular) system RC666-701 Huriye Ercan Waltraud Cornelia Schrottmaier Anita Pirabe Anna Schmuckenschlager David Pereyra David Pereyra Jonas Santol Jonas Santol Erich Pawelka Marianna T. Traugott Christian Schörgenhofer Tamara Seitz Mario Karolyi Jae-Won Yang Bernd Jilma Alexander Zoufaly Alice Assinger Maria Zellner Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| description |
Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional and biochemical profile in patients with COVID-19 in dependence of mortality within 5-days after hospitalization.Methods: The COVID-19-related platelet phenotype was examined by analyzing their basal activation state via integrin αIIbβ3 activation using flow cytometry and the proteome by unbiased two-dimensional differential in-gel fluorescence electrophoresis. In total we monitored 98 surviving and 12 non-surviving COVID-19 patients over 5 days of hospital stay and compared them to healthy controls (n = 12).Results: Over the observation period the level of basal αIIbβ3 activation on platelets from non-surviving COVID-19 patients decreased compared to survivors. In line with this finding, proteomic analysis revealed a decrease in the total amount of integrin αIIb (ITGA2B), a subunit of αIIbβ3, in COVID-19 patients compared to healthy controls; the decline was even more pronounced for the non-survivors. Consumption of the fibrin-stabilizing factor coagulation factor XIIIA (F13A1) was higher in platelets from COVID-19 patients and tended to be higher in non-survivors; plasma concentrations of the latter also differed significantly. Depending on COVID-19 disease status and mortality, increased amounts of annexin A5 (ANXA5), eukaryotic initiation factor 4A-I (EIF4A1), and transaldolase (TALDO1) were found in the platelet proteome and also correlated with the nasopharyngeal viral load. Dysregulation of these proteins may play a role for virus replication. ANXA5 has also been identified as an autoantigen of the antiphospholipid syndrome, which is common in COVID-19 patients. Finally, the levels of two different protein disulfide isomerases, P4HB and PDIA6, which support thrombosis, were increased in the platelets of COVID-19 patients.Conclusion: Platelets from COVID-19 patients showed significant changes in the activation phenotype, in the processing of the final coagulation factor F13A1 and the phospholipid-binding protein ANXA5 compared to healthy subjects. Additionally, these results demonstrate specific alterations in platelets during COVID-19, which are significantly linked to fatal outcome. |
| format |
article |
| author |
Huriye Ercan Waltraud Cornelia Schrottmaier Anita Pirabe Anna Schmuckenschlager David Pereyra David Pereyra Jonas Santol Jonas Santol Erich Pawelka Marianna T. Traugott Christian Schörgenhofer Tamara Seitz Mario Karolyi Jae-Won Yang Bernd Jilma Alexander Zoufaly Alice Assinger Maria Zellner |
| author_facet |
Huriye Ercan Waltraud Cornelia Schrottmaier Anita Pirabe Anna Schmuckenschlager David Pereyra David Pereyra Jonas Santol Jonas Santol Erich Pawelka Marianna T. Traugott Christian Schörgenhofer Tamara Seitz Mario Karolyi Jae-Won Yang Bernd Jilma Alexander Zoufaly Alice Assinger Maria Zellner |
| author_sort |
Huriye Ercan |
| title |
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| title_short |
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| title_full |
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| title_fullStr |
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| title_full_unstemmed |
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5 |
| title_sort |
platelet phenotype analysis of covid-19 patients reveals progressive changes in the activation of integrin αiibβ3, f13a1, the sars-cov-2 target eif4a1 and annexin a5 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/3b745cc794fd43db9f5982030c9086d2 |
| work_keys_str_mv |
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