Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

Frontiers in Immunology

Siebe G. Blok¹  Anno Saris¹  Lilian J. Meijboom¹  Harm Jan Bogaard¹  Esther J. Nossent²  JanWillem Duitman²  René Lutter²  Alex R. Schuurman³  Ilse Jongerius³  Tom D.Y. Reijnders⁴  Anton Vonk Noordegraaf⁴  Tom van der Poll⁷  Leo Heunks⁸  Heder de Vries^1,10 

[1] Immunity Institute, Amsterdam UMC, Amsterdam, Netherlands;Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, Netherlands;;Amsterdam Infection &Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands;Department of Experimental Immunology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands;Department of Immunopathology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands;Department of Intensive Care Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands;Department of Pulmonary Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands;Department of Radiology and Nuclear Medicine, Amsterdam UMC, Free University Amsterdam, Amsterdam, Netherlands;Emma Children’s Hospital, Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands;

关键词: COVID-19;    persistent ARDS;    coagulation;    innate immune response;    bronchoalveolar space;   

DOI  :  10.3389/fimmu.2021.664209

来源: DOAJ

【 摘 要 】

RationaleSystemic 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.ObjectivesTo evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.MethodsPaired 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 ResultsIn 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.ConclusionsCritically 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.

【 授权许可】

Unknown