Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients
Copyright © 2021 Nossent, Schuurman, Reijnders, Saris, Jongerius, Blok, de Vries, Duitman, Vonk Noordegraaf, Meijboom, Lutter, Heunks, Bogaard and van der Poll..
Rationale: Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.
Objectives: To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.
Methods: Paired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.
Measurements and Main Results: In all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.
Conclusions: Critically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory "storm" in severe COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Frontiers in immunology - 12(2021) vom: 31., Seite 664209 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nossent, Esther J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.06.2021 Date Revised 07.06.2021 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2021.664209 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326034773 |
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| 100 | 1 | |a Nossent, Esther J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients |
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| 500 | |a Date Revised 07.06.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Nossent, Schuurman, Reijnders, Saris, Jongerius, Blok, de Vries, Duitman, Vonk Noordegraaf, Meijboom, Lutter, Heunks, Bogaard and van der Poll. | ||
| 520 | |a Rationale: Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited | ||
| 520 | |a Objectives: To evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome | ||
| 520 | |a Methods: Paired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured | ||
| 520 | |a Measurements and Main Results: In all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined | ||
| 520 | |a Conclusions: Critically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory "storm" in severe COVID-19 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a bronchoalveolar space | |
| 650 | 4 | |a coagulation | |
| 650 | 4 | |a innate immune response | |
| 650 | 4 | |a persistent ARDS | |
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| 700 | 1 | |a Schuurman, Alex R |e verfasserin |4 aut | |
| 700 | 1 | |a Reijnders, Tom D Y |e verfasserin |4 aut | |
| 700 | 1 | |a Saris, Anno |e verfasserin |4 aut | |
| 700 | 1 | |a Jongerius, Ilse |e verfasserin |4 aut | |
| 700 | 1 | |a Blok, Siebe G |e verfasserin |4 aut | |
| 700 | 1 | |a de Vries, Heder |e verfasserin |4 aut | |
| 700 | 1 | |a Duitman, JanWillem |e verfasserin |4 aut | |
| 700 | 1 | |a Vonk Noordegraaf, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Meijboom, Lilian J |e verfasserin |4 aut | |
| 700 | 1 | |a Lutter, René |e verfasserin |4 aut | |
| 700 | 1 | |a Heunks, Leo |e verfasserin |4 aut | |
| 700 | 1 | |a Bogaard, Harm Jan |e verfasserin |4 aut | |
| 700 | 1 | |a van der Poll, Tom |e verfasserin |4 aut | |
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