TY - JOUR
T1 - Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients
AU - Nossent, Esther J.
AU - Schuurman, Alex R.
AU - Reijnders, Tom D. Y.
AU - Saris, Anno
AU - Jongerius, Ilse
AU - Blok, Siebe G.
AU - de Vries, Heder
AU - Duitman, JanWillem
AU - Vonk Noordegraaf, Anton
AU - Meijboom, Lilian J.
AU - Lutter, René
AU - Heunks, Leo
AU - Bogaard, Harm Jan
AU - the ArtDECO consortium and the Amsterdam UMC COVID study group
AU - van der Poll, Tom
N1 - Funding Information: The authors would like to thank Hella Aberson and Regina de Beer from the Center for Experimental and Molecular Medicine, Tamara Dekker and Barbara Dierdorp from the Department of Experimental Immunology for their technical support in the execution and analysis of the biomarker assays, Yanaika S. Sabogal Pineros from the Department of Experimental Immunology for performing the RILCO and RILCA studies, Gerard van Mierlo, Angela Kamp and Dorina Roem from Sanquin for their technical support in the execution and analysis of the complement assays, and also Jarne van Hattem and Frank van Someren from the department of Medical Microbiology for the clinical PCR data. On behalf of the ArtDECO consortium: EN, JD, AS, HV, LM, Lieuwe D. Bos, SB, AS, TR, Juan J. Garcia Vallejo, Hetty Bontkes, Alexander P.J. Vlaar, Joost Wiersinga, RL, TP, HB, and LH. On behalf of the Amsterdam UMC COVID study group: S. de Bruin, ARS, R. Koning, M. van Agtmael, A.G. Algera, F. van Baarle, D. Bax, M. Beudel, HB, M. Bomers, P.I. Bonta, L. Bos, M. Botta, J. de Brabander, G. de Bree, M. Bugiani, E. Bulle, O. Chouchane, A. Cloherty, D.A. Dongelmans, P. Elbers, L. Fleuren, S. Geerlings, B. Geerts, T. Geijtenbeek, A. Girbes, J.A. Goorhuis, M.P. Grobusch, F. Hafkamp, L. Hagens, J. Hamann, V. Harris, R. Hemke, S.M. Hermans, LH, M. Hollmann, J. Horn, J.W. Hovius, M.D. de Jong, M. van Mourik, J. Nellen, EN, F. Paulus, TR, TP, B. Preckel, J.M. Prins, J. Raasveld, M. Schinkel, M. Schultz, K. Sigaloff, M. Smit, C.S. Stijnis, W. Stilma, C. Teunissen, P. Thoral, A. Tsonas, M. van der Valk, D. Veelo, HV, M. van Vugt, D. Wouters, A.H. Zwinderman, M.C. Brouwer, W.J. Wiersinga, A.P.J. Vlaar and D. van de Beek. Funding Information: TR and AS are supported by the research program NACTAR (Novel Antibiotic Compounds and Therapies Antagonizing Publisher Copyright: © Copyright © 2021 Nossent, Schuurman, Reijnders, Saris, Jongerius, Blok, de Vries, Duitman, Vonk Noordegraaf, Meijboom, Lutter, Heunks, Bogaard and van der Poll. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/14
Y1 - 2021/5/14
N2 - 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.
AB - 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.
KW - COVID-19
KW - bronchoalveolar space
KW - coagulation
KW - innate immune response
KW - persistent ARDS
UR - http://www.scopus.com/inward/record.url?scp=85107038160&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2021.664209
DO - https://doi.org/10.3389/fimmu.2021.664209
M3 - Article
C2 - 34054832
SN - 1664-3224
VL - 12
SP - 664209
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 664209
ER -