TY - JOUR
T1 - Clinical features and prognostic factors in Covid-19
T2 - A prospective cohort study
AU - de Bruin, Sanne
AU - Bos, Lieuwe D.
AU - van Roon, Marian A.
AU - Tuip-de Boer, Anita M.
AU - Schuurman, Alex R.
AU - Koel-Simmelinck, Marleen J.A.
AU - Bogaard, Harm Jan
AU - Tuinman, Pieter Roel
AU - van Agtmael, Michiel A.
AU - Hamann, Jörg
AU - Teunissen, Charlotte E.
AU - Wiersinga, W. Joost
AU - (Koos) Zwinderman, A. H.
AU - Brouwer, Matthijs C.
AU - van de Beek, Diederik
AU - Vlaar, Alexander P.J.
AU - Amsterdam UMC COVDI-19 Biobank Investigators
AU - Bugiani, M
AU - Amsterdam UMC COVID-19 Biobank Investigators
AU - Study group members AMC, null
AU - Hollmann, Markus W.
AU - Preckel, Prof. dr. , Benedikt
AU - Veelo, Denise P.
AU - Study group members AMC, null
AU - Harris, Vanessa C.
N1 - Funding Information: This study was funded by the Amsterdam UMC, Amsterdam UMC Corona Reseach Fund, and Dr. C.J. Vaillant Fonds (to DvdB). We would like to thank all medical, paramedical, laboratory and nursing staff involved in the care of the COVD-19 patients for making it possible to build the Amsterdam UMC COVID-19 Biobank Cov in the middle of the COVID-19 outbreak in The Netherlands. Michiel van Agtmael2, Anne Geke Algera1, Brent Appelman2, Frank van Baarle1, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers2 Peter Bonta5, Lieuwe Bos1, Michela Botta1, Justin de Brabander2, Godelieve de Bree2, Sanne de Bruin1, David T.P. Buis1, Marianna Bugiani5, Esther Bulle1, Nora Chekrouni4, Osoul Chouchane2 Alex Cloherty3, Mirjam Dijkstra12, Dave A. Dongelmans1, Romein W.G. Dujardin1, Paul Elbers1, Lucas Fleuren1, Suzanne Geerlings2 Theo Geijtenbeek3, Armand Girbes1, Bram Goorhuis2, Martin P. Grobusch2, Florianne Hafkamp3, Laura Hagens1, Jorg Hamann7, Vanessa Harris2, Robert Hemke8, Sabine M. Hermans2 Leo Heunks1, Markus Hollmann6, Janneke Horn1, Joppe W. Hovius2, Menno D. de Jong9, Rutger Koning4, Endry H.T. Lim1, Niels van Mourik1, Jeaninne Nellen2, Esther J. Nossent5, Sabine Olie4, Frederique Paulus1, Edgar Peters2, Dan A.I. Pina-Fuentes4, Tom van der Poll2, Bennedikt Preckel6, Jan M. Prins2, Jorinde Raasveld1, Tom Reijnders2, Maurits C.F.J. de Rotte12, Michiel Schinkel2, Marcus J. Schultz1, Femke A.P. Schrauwen12, Alex Schuurmans10, Jaap Schuurmans1, Kim Sigaloff1, Marleen A. Slim1,2, Patrick Smeele5, Marry Smit1, Cornelis S. Stijnis2, Willemke Stilma1, Charlotte Teunissen11, Patrick Thoral1, Anissa M Tsonas1, Pieter R. Tuinman2, Marc van der Valk2, Denise Veelo6, Carolien Volleman1, Heder de Vries1, Lonneke A. Vught1,2, Mich?le van Vugt2, Dorien Wouters12, A. H (Koos) Zwinderman13, Matthijs C. Brouwer4, W. Joost Wiersinga2, Alexander P.J. Vlaar1, Diederik van de Beek (d.vandebeek@amsterdamumc.nl)4. 1Department of Intensive Care, Amsterdam UMC, Amsterdam, The Netherlands; 2Department of Infectious Diseases, Amsterdam UMC, Amsterdam, The Netherlands; 3Experimental Immunology, Amsterdam UMC, Amsterdam, The Netherlands; 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, The Netherlands; 5Department of Pulmonology, Amsterdam UMC, Amsterdam, The Netherlands; 6Department of Anesthesiology, Amsterdam UMC, Amsterdam, The Netherlands; 7Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, The Netherlands; 8Department of Radiology, Amsterdam UMC, Amsterdam, The Netherlands; 9Department of Medical Microbiology, Amsterdam UMC, Amsterdam, The Netherlands; 10Department of Internal Medicine, Amsterdam UMC, Amsterdam, The Netherlands; 11Neurochemical Laboratory, Amsterdam UMC, Amsterdam, The Netherlands; 12Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, The Netherlands; 13Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, The Netherlands. Publisher Copyright: © 2021 The Author(s)
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality. Findings: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest–specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids. Interpretation: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19. Funding: Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.
AB - Background: Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods: We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality. Findings: A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest–specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids. Interpretation: Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19. Funding: Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.
KW - Biomarker
KW - COVID-19
KW - Clinical features
KW - Pathway analysis
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85105920427&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ebiom.2021.103378
DO - https://doi.org/10.1016/j.ebiom.2021.103378
M3 - Article
C2 - 34000622
SN - 2352-3964
VL - 67
SP - 103378
JO - eBioMedicine
JF - eBioMedicine
M1 - 103378
ER -