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Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19 : a substudy of the phase 2 PANAMO trial. / Lim, Endry H. T.; Vlaar, Alexander P. J.; Bos, Lieuwe D. J. et al.

In: Respiratory research, Vol. 23, No. 1, 375, 01.12.2022.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Lim, EHT, Vlaar, APJ, Bos, LDJ, van Vught, LA, Boer, AMT, Dujardin, RWG, Habel, M, Xu, Z, Brouwer, MC, van de Beek, D, de Bruin, S, the Amsterdam UMC COVID-19 Biobank Investigators, van Agtmael, M, Algera, AG, Appelman, B, van Baarle, F, Beudel, M, Bogaard, HJ, Bomers, M, Bonta, P, Botta, M, de Brabander, J, Bree, G, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Buis, DTP, de Rotte, MCFJ, Dijkstra, M, Dongelmans, DA, Elbers, P, Fleuren, L, Geerlings, S, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, MP, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, SM, Heunks, L, Hollmann, M, Horn, J, Hovius, JW, de Jong, MD, Koning, R, van Mourik, N, Nellen, J, Nossent, EJ, Paulus, F, Peters, E, Piña-Fuentes, DAI, van der Poll, T, Preckel, B, Prins, JM, Raasveld, J, Reijnders, T, Schinkel, M, Schrauwen, FAP, Schultz, MJ, Schuurman, A, Schuurmans, J, Sigaloff, K, Slim, MA, Smeele, P, Smit, M, Stijnis, CS, Stilma, W, Teunissen, C, Thoral, P, Tsonas, AM, Tuinman, PR, van der Valk, M, Veelo, D, Volleman, C, de Vries, H, van Vugt, M, Wouters, D, Zwinderman, AH & Wiersinga, WJ 2022, 'Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial', Respiratory research, vol. 23, no. 1, 375. https://doi.org/10.1186/s12931-022-02278-1

APA

Lim, E. H. T., Vlaar, A. P. J., Bos, L. D. J., van Vught, L. A., Boer, A. M. T., Dujardin, R. W. G., Habel, M., Xu, Z., Brouwer, M. C., van de Beek, D., de Bruin, S., the Amsterdam UMC COVID-19 Biobank Investigators, van Agtmael, M., Algera, A. G., Appelman, B., van Baarle, F., Beudel, M., Bogaard, H. J., Bomers, M., ... Wiersinga, W. J. (2022). Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial. Respiratory research, 23(1), [375]. https://doi.org/10.1186/s12931-022-02278-1

Vancouver

Lim EHT, Vlaar APJ, Bos LDJ, van Vught LA, Boer AMT, Dujardin RWG et al. Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial. Respiratory research. 2022 Dec 1;23(1):375. doi: 10.1186/s12931-022-02278-1

Author

Lim, Endry H. T. ; Vlaar, Alexander P. J. ; Bos, Lieuwe D. J. et al. / Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19 : a substudy of the phase 2 PANAMO trial. In: Respiratory research. 2022 ; Vol. 23, No. 1.

BibTeX

@article{dca896a832934de88947c8841368cccb,
title = "Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial",
abstract = "We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted.",
keywords = "C5a, COVID-19, Complement, Complement inhibition, SARS-CoV-2, Vilobelimab",
author = "Lim, {Endry H. T.} and Vlaar, {Alexander P. J.} and Bos, {Lieuwe D. J.} and {van Vught}, {Lonneke A.} and Boer, {Anita M. Tuip-de} and Dujardin, {Romein W. G.} and Maria Habel and Zhongli Xu and Brouwer, {Matthijs C.} and {van de Beek}, Diederik and {de Bruin}, Sanne and {the Amsterdam UMC COVID-19 Biobank Investigators} and {van Agtmael}, Michiel and Algera, {Anne Geke} and Brent Appelman and {van Baarle}, Floor and Martijn Beudel and Bogaard, {Harm Jan} and Marije Bomers and Peter Bonta and Michela Botta and {de Brabander}, Justin and Godelieve Bree and Marianna Bugiani and Esther Bulle and Osoul Chouchane and Alex Cloherty and Buis, {David T. P.} and {de Rotte}, {Maurits C. F. J.} and Mirjam Dijkstra and Dongelmans, {Dave A.} and Paul Elbers and Lucas Fleuren and Suzanne Geerlings and Theo Geijtenbeek and Armand Girbes and Bram Goorhuis and Grobusch, {Martin P.} and Laura Hagens and Jorg Hamann and Vanessa Harris and Robert Hemke and Hermans, {Sabine M.} and Leo Heunks and Markus Hollmann and Janneke Horn and Hovius, {Joppe W.} and {de Jong}, {Menno D.} and Rutger Koning and {van Mourik}, Niels and Jeannine Nellen and Nossent, {Esther J.} and Frederique Paulus and Edgar Peters and Pi{\~n}a-Fuentes, {Dan A. I.} and {van der Poll}, Tom and Bennedikt Preckel and Prins, {Jan M.} and Jorinde Raasveld and Tom Reijnders and Michiel Schinkel and Schrauwen, {Femke A. P.} and Schultz, {Marcus J.} and Alex Schuurman and Jaap Schuurmans and Kim Sigaloff and Slim, {Marleen A.} and Patrick Smeele and Marry Smit and Stijnis, {Cornelis S.} and Willemke Stilma and Charlotte Teunissen and Patrick Thoral and Tsonas, {Anissa M.} and Tuinman, {Pieter R.} and {van der Valk}, Marc and Denise Veelo and Carolien Volleman and {de Vries}, Heder and {van Vugt}, Mich{\`e}le and Dorien Wouters and Zwinderman, {Aeilko H.} and Wiersinga, {W. Joost}",
note = "Funding Information: The phase 2 PANAMO trial was funded by InflaRx. The Amsterdam UMC COVID-19 biobank was funded by the Amsterdam UMC, Amsterdam UMC Corona Research Fund, and Dr. C. J. Vaillant Fonds for DB, paid to Amsterdam UMC. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "10.1186/s12931-022-02278-1",
language = "English",
volume = "23",
journal = "Respiratory research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19

T2 - a substudy of the phase 2 PANAMO trial

AU - Lim, Endry H. T.

AU - Vlaar, Alexander P. J.

AU - Bos, Lieuwe D. J.

AU - van Vught, Lonneke A.

AU - Boer, Anita M. Tuip-de

AU - Dujardin, Romein W. G.

AU - Habel, Maria

AU - Xu, Zhongli

AU - Brouwer, Matthijs C.

AU - van de Beek, Diederik

AU - de Bruin, Sanne

AU - the Amsterdam UMC COVID-19 Biobank Investigators

AU - van Agtmael, Michiel

AU - Algera, Anne Geke

AU - Appelman, Brent

AU - van Baarle, Floor

AU - Beudel, Martijn

AU - Bogaard, Harm Jan

AU - Bomers, Marije

AU - Bonta, Peter

AU - Botta, Michela

AU - de Brabander, Justin

AU - Bree, Godelieve

AU - Bugiani, Marianna

AU - Bulle, Esther

AU - Chouchane, Osoul

AU - Cloherty, Alex

AU - Buis, David T. P.

AU - de Rotte, Maurits C. F. J.

AU - Dijkstra, Mirjam

AU - Dongelmans, Dave A.

AU - Elbers, Paul

AU - Fleuren, Lucas

AU - Geerlings, Suzanne

AU - Geijtenbeek, Theo

AU - Girbes, Armand

AU - Goorhuis, Bram

AU - Grobusch, Martin P.

AU - Hagens, Laura

AU - Hamann, Jorg

AU - Harris, Vanessa

AU - Hemke, Robert

AU - Hermans, Sabine M.

AU - Heunks, Leo

AU - Hollmann, Markus

AU - Horn, Janneke

AU - Hovius, Joppe W.

AU - de Jong, Menno D.

AU - Koning, Rutger

AU - van Mourik, Niels

AU - Nellen, Jeannine

AU - Nossent, Esther J.

AU - Paulus, Frederique

AU - Peters, Edgar

AU - Piña-Fuentes, Dan A. I.

AU - van der Poll, Tom

AU - Preckel, Bennedikt

AU - Prins, Jan M.

AU - Raasveld, Jorinde

AU - Reijnders, Tom

AU - Schinkel, Michiel

AU - Schrauwen, Femke A. P.

AU - Schultz, Marcus J.

AU - Schuurman, Alex

AU - Schuurmans, Jaap

AU - Sigaloff, Kim

AU - Slim, Marleen A.

AU - Smeele, Patrick

AU - Smit, Marry

AU - Stijnis, Cornelis S.

AU - Stilma, Willemke

AU - Teunissen, Charlotte

AU - Thoral, Patrick

AU - Tsonas, Anissa M.

AU - Tuinman, Pieter R.

AU - van der Valk, Marc

AU - Veelo, Denise

AU - Volleman, Carolien

AU - de Vries, Heder

AU - van Vugt, Michèle

AU - Wouters, Dorien

AU - Zwinderman, Aeilko H.

AU - Wiersinga, W. Joost

N1 - Funding Information: The phase 2 PANAMO trial was funded by InflaRx. The Amsterdam UMC COVID-19 biobank was funded by the Amsterdam UMC, Amsterdam UMC Corona Research Fund, and Dr. C. J. Vaillant Fonds for DB, paid to Amsterdam UMC. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted.

AB - We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted.

KW - C5a

KW - COVID-19

KW - Complement

KW - Complement inhibition

KW - SARS-CoV-2

KW - Vilobelimab

UR - http://www.scopus.com/inward/record.url?scp=85144636825&partnerID=8YFLogxK

U2 - 10.1186/s12931-022-02278-1

DO - 10.1186/s12931-022-02278-1

M3 - Article

C2 - 36566174

VL - 23

JO - Respiratory research

JF - Respiratory research

SN - 1465-9921

IS - 1

M1 - 375

ER -

ID: 29085632