Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19
Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2023-11-01
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| Series: | Journal of Innate Immunity |
| Subjects: | |
| Online Access: | https://beta.karger.com/Article/FullText/533339 |
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| author | Tiphaine Ruggeri Yasmin De Wit Noëlia Schärz Gerard van Mierlo Anne Angelillo-Scherrer Justine Brodard Joerg C. Schefold Cédric Hirzel Ilse Jongerius Sacha Zeerleder |
| author_facet | Tiphaine Ruggeri Yasmin De Wit Noëlia Schärz Gerard van Mierlo Anne Angelillo-Scherrer Justine Brodard Joerg C. Schefold Cédric Hirzel Ilse Jongerius Sacha Zeerleder |
| author_sort | Tiphaine Ruggeri |
| collection | DOAJ |
| description | Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19. |
| first_indexed | 2024-03-09T02:12:59Z |
| format | Article |
| id | doaj.art-ae26b382323c41bab2ef5ee6c738dcc9 |
| institution | Directory Open Access Journal |
| issn | 1662-8128 |
| language | English |
| last_indexed | 2024-03-09T02:12:59Z |
| publishDate | 2023-11-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-ae26b382323c41bab2ef5ee6c738dcc92023-12-07T07:19:14ZengKarger PublishersJournal of Innate Immunity1662-81282023-11-0115185086410.1159/000533339533339Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19Tiphaine Ruggeri0Yasmin De Wit1Noëlia Schärz2Gerard van Mierlo3Anne Angelillo-Scherrer4Justine Brodard5Joerg C. Schefold6Cédric Hirzel7Ilse Jongerius8Sacha Zeerleder9Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment of Immunopathology, Sanquin Research, Amsterdam, The NetherlandsDepartment of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment of Immunopathology, Sanquin Research, Amsterdam, The NetherlandsDepartment of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Immunopathology, Sanquin Research, Amsterdam, The NetherlandsDepartment of Hematology, Kantonsspital Luzern, Lucerne and University of Bern, Bern, SwitzerlandSevere COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19.https://beta.karger.com/Article/FullText/533339thrombosiscell-free dnacomplement activationcovid-19neutrophil activation |
| spellingShingle | Tiphaine Ruggeri Yasmin De Wit Noëlia Schärz Gerard van Mierlo Anne Angelillo-Scherrer Justine Brodard Joerg C. Schefold Cédric Hirzel Ilse Jongerius Sacha Zeerleder Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 Journal of Innate Immunity thrombosis cell-free dna complement activation covid-19 neutrophil activation |
| title | Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 |
| title_full | Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 |
| title_fullStr | Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 |
| title_full_unstemmed | Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 |
| title_short | Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19 |
| title_sort | immunothrombosis and complement activation contribute to disease severity and adverse outcome in covid 19 |
| topic | thrombosis cell-free dna complement activation covid-19 neutrophil activation |
| url | https://beta.karger.com/Article/FullText/533339 |
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