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 - van de Beek, Diederik
AU - the Amsterdam UMC COVID-19 Biobank Investigators
AU - van Agtmael, Michiel
AU - Beudel, Martijn
AU - Bogaard, Harm Jan
AU - Bomers, Marije
AU - Bonta, Peter
AU - de Brabander, Justin
AU - Bugiani, Marianna
AU - Chouchane, Osoul
AU - Buis, David T. P.
AU - Elbers, Paul
AU - Fleuren, Lucas
AU - Geerlings, Suzanne
AU - Geijtenbeek, Theo
AU - Girbes, Armand
AU - Grobusch, Martin P.
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 - Nossent, Esther J.
AU - Peters, Edgar
AU - van der Poll, Tom
AU - Prins, Jan M.
AU - Reijnders, Tom
AU - Schinkel, Michiel
AU - Schuurman, Alex
AU - Schuurmans, Jaap
AU - Sigaloff, Kim
AU - Smeele, Patrick
AU - Teunissen, Charlotte
AU - Thoral, Patrick
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 - Wiersinga, W. Joost
AU - Dujardin, Romein W. G.
AU - Brouwer, Matthijs C.
AU - de Bruin, Sanne
AU - Appelman, Brent
AU - Botta, Michela
AU - Bulle, Esther
AU - Cloherty, Alex
AU - de Rotte, Maurits C. F. J.
AU - Dijkstra, Mirjam
AU - Dongelmans, Dave A.
AU - Goorhuis, Bram
AU - Hagens, Laura
AU - Hamann, Jorg
AU - Nellen, Jeannine
AU - Paulus, Frederique
AU - Piña-Fuentes, Dan A. I.
AU - Raasveld, Jorinde
AU - Schrauwen, Femke A. P.
AU - Schultz, Marcus J.
AU - Slim, Marleen A.
AU - Smit, Marry
AU - Stijnis, Cornelis S.
AU - Stilma, Willemke
AU - Tsonas, Anissa M.
AU - Zwinderman, Aeilko H.
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 - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85144636825&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36566174
UR - http://www.scopus.com/inward/record.url?scp=85144636825&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12931-022-02278-1
DO - https://doi.org/10.1186/s12931-022-02278-1
M3 - Comment/Letter to the editor
C2 - 36566174
SN - 1465-9921
VL - 23
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 375
ER -