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Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients.
Nossent, Esther J; Schuurman, Alex R; Reijnders, Tom D Y; Saris, Anno; Jongerius, Ilse; Blok, Siebe G; de Vries, Heder; Duitman, JanWillem; Vonk Noordegraaf, Anton; Meijboom, Lilian J; Lutter, René; Heunks, Leo; Bogaard, Harm Jan; van der Poll, Tom.
  • Nossent EJ; Department of Pulmonary Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands.
  • Schuurman AR; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, Netherlands.
  • Reijnders TDY; Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
  • Saris A; Amsterdam Infection & Immunity Institute, Amsterdam UMC, Amsterdam, Netherlands.
  • Jongerius I; Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
  • Blok SG; Amsterdam Infection & Immunity Institute, Amsterdam UMC, Amsterdam, Netherlands.
  • de Vries H; Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
  • Duitman J; Amsterdam Infection & Immunity Institute, Amsterdam UMC, Amsterdam, Netherlands.
  • Vonk Noordegraaf A; Department of Immunopathology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  • Meijboom LJ; Emma Children's Hospital, Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
  • Lutter R; Department of Pulmonary Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands.
  • Heunks L; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, Netherlands.
  • Bogaard HJ; Department of Intensive Care Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands.
  • van der Poll T; Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Front Immunol ; 12: 664209, 2021.
Article in English | MEDLINE | ID: covidwho-1247863
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Thromboplastin / Critical Illness / SARS-CoV-2 / COVID-19 / Lung Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.664209

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Thromboplastin / Critical Illness / SARS-CoV-2 / COVID-19 / Lung Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.664209