@article{5e32eb93ca974a9685a8111037f621c2,
title = "Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19",
abstract = "Endotheliopathy plays a role in the development of acute kidney and lung injury in COVID-19, probably due to inflammation, endothelial permeability, vascular leakage and edema formation. This study examined alterations in the circulation of patients with mild and severe COVID-19 on in vitro endothelial permeability and its relation to the endothelial angiopoietin/Tie2 system, which is involved in the regulation of endothelial permeability. Plasma was obtained from COVID-19 patients admitted to the ward (n = 14) or ICU (n = 20) at admission and after 1 and 2 weeks and healthy controls (n = 5). Human kidney and lung endothelial cells were exposed to patient plasma and treated with recombinant angiopoietin-1. In vitro endothelial barrier function was assessed using electric cell-substrate impedance sensing. Circulating markers of the angiopoietin/Tie2 system, endothelial dysfunction and glycocalyx degradation were measured by ELISA. Plasma from COVID-19 patients reduced endothelial resistance compared to healthy controls, but COVID-19 plasma-induced drop in endothelial resistance did not differ between ward and ICU patients. Circulating angiopoietin-2, soluble Tie2 and soluble Tie1 levels increased over time in ICU patients, whereas levels remained stable in ward patients. The increase in angiopoietin-2 was able to predict 90-day mortality (AUC = 0.914, p < 0.001). Treatment with recombinant angiopoietin-1 did not restore COVID-19 plasma-induced hyperpermeability. In conclusion, these results suggest that indirect effects of the virus represented in the circulation of COVID-19 patients induced endothelial hyperpermeability irrespective of disease severity and changes in the endothelial angiopoietin/Tie2 system. Nonetheless, angiopoietin-2 might be of interest in the context of organ injury and patient outcome in COVID-19.",
keywords = "Angiopoietin-2, COVID-19, Electric impedance, Endothelial cells, Permeability",
author = "Carolien Volleman and Roselique Ibelings and Vlaar, {Alexander P. J.} and {van den Brom}, {Charissa E.} and {the Amsterdam UMC COVID-19 biobank study group} and {van Agtmael}, {M. A.} and Algera, {A. G.} and {van Amstel}, R. and B. Appelman and {van Baarle}, {F. E. H. P.} and M. Beudel and M. Bomers and Bonta, {P. I.} and Bos, {L. D. J.} and {de Brabander}, J. and {de Bruin}, S. and M. Bugiani and O. Chouchane and M. Dijkstra and Fleuren, {L. M.} and Geerlings, {S. E.} and Geijtenbeek, {T. B. H.} and Girbes, {A. R. J.} and A. Goorhuis and Grobusch, {M. P.} and R. Hemke and Heunks, {L. M. A.} and J. Horn and Hovius, {J. W.} and R. Koning and Lim, {E. H. T.} and {van Mourik}, N. and Nossent, {E. J.} and E. Peters and B. Preckel and Prins, {J. M.} and Reijnders, {T. D. Y.} and M. Schinkel and Schuurman, {A. R.} and J. Schuurmans and K. Sigaloff and P. Smeele and Smit, {M. R.} and C. Stijnis and Teunissen, {C. E.} and P. Thoral and Tuinman, {P. R.} and C. Volleman and {van Vugt}, M. and D. Wouters and Wiersinga, {W. J.} and Bax, {D. J. C.} and M. Botta and {de Bree}, {G. J.} and D. Buis and Bulle, {E. B.} and Cloherty, {A. P. M.} and {de Rotte}, {M. C. F. J.} and Dongelmans, {D. A.} and Hafkamp, {F. M. J.} and Hagens, {L. A.} and J. Hamann and Harris, {V. C.} and Hermans, {S. M.} and Hollmann, {M. W.} and {de Jong}, {M. D.} and Nellen, {J. F.} and F. Paulus and Raasveld, {S. J.} and Schrauwen, {F. A. P.} and Schultz, {M. J.} and Slim, {M. A.} and W. Stilma and Tsonas, {A. M.} and Veelo, {D. P.} and {van Vught}, {L. A.} and Zwinderman, {A. H.} and Brouwer, {M. C.}",
note = "Funding Information: CEvdB is financially supported by the European Society of Intensive Care Medicine (Levi-Montalcini Award 2017), the Dutch Society of Anesthesiology (Young Investigator Grant 2017), and the Dutch Research Council (Veni 2019). The remaining authors are financially supported by their department. No financial support was provided from industrial companies. Funding Information: We would like to thank all medical, paramedical, laboratory and nursing staff involved in the care of the COVID-19 patients for making it possible to build the Amsterdam UMC COVID-19 Biobank in The Netherlands. The Amsterdam UMC COVID-19 Biobank Study Group: M.A. van Agtmael2, A.G. Algera1, R. van Amstel1, B. Appelman2, F.E.H.P. van Baarle1, D.J.C. Bax3, M. Beudel4, H.J. Boogaard5, M. Bomers2, P.I. Bonta5, L.D.J. Bos1, M. Botta1, J. de Brabander2, G.J. de Bree2, S. de Bruin1, M. Bugiani5, D. Buis1, E.B. Bulle1, O. Chouchane2, A.P.M. Cloherty3, M.C.F.J. de Rotte12, M. Dijkstra12, D.A. Dongelmans1, R.W.G. Dujardin1, P.E. Elbers1, L.M. Fleuren1, S.E. Geerlings2, T.B.H. Geijtenbeek3, A.R.J. Girbes1, A. Goorhuis2, M.P. Grobusch2, F.M.J. Hafkamp3, L.A. Hagens1, J. Hamann7, V.C. Harris2, R. Hemke8, S.M. Hermans2, L.M.A. Heunks1, M.W. Hollmann6, J. Horn1, J.W. Hovius2, M.D. de Jong9, R. Koning4, E.H.T. Lim1, N. van Mourik1, J.F. Nellen2, E.J. Nossent5, F. Paulus1, E. Peters2, D. Pi{\~n}a-Fuentes4, T. van der Poll2, B. Preckel6, J.M. Prins2, S.J. Raasveld1, T.D.Y. Reijnders2, M. Schinkel2, F.A.P. Schrauwen12, M.J. Schultz1, A.R. Schuurman10, J. Schuurmans1, K. Sigaloff1, M.A. Slim1,2, P. Smeele5, M.R. Smit1, C. Stijnis2, W. Stilma1, C.E. Teunissen11, P. Thoral1, A.M. Tsonas1, P.R. Tuinman1, M. van der Valk2, D.P. Veelo6, C. Volleman1, H. de Vries1, L.A. van Vught1,2, M. van Vugt2, D. Wouters12, A.H. Zwinderman13, M.C. Brouwer4, W.J. Wiersinga2, A.P.J. Vlaar1, D. van Beek4.1Department 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: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = sep,
day = "1",
doi = "https://doi.org/10.1007/s44200-023-00036-2",
language = "English",
volume = "29",
pages = "83--93",
journal = "Artery Research",
issn = "1872-9312",
publisher = "Elsevier BV",
number = "3",
}