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

Correspondence

Lonneke A. van Vught¹  Anita M. Tuip-de Boer²  Alexander P. J. Vlaar²  Sanne de Bruin²  Romein W. G. Dujardin²  Lieuwe D. J. Bos²  Endry H. T. Lim³  Matthijs C. Brouwer⁴  Diederik van de Beek⁴  Maria Habel⁵  Zhongli Xu⁵ 

[1] Department of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands;Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands;Department of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands;Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Amsterdam, The Netherlands;Department of Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands;Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Amsterdam, The Netherlands;Department of Neurology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands;Amsterdam Neuroscience, Amsterdam, The Netherlands;Department of Intensive Care Medicine, Amsterdam UMC, Location AMC, Room C3-421, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands;Department of Neurology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands;Amsterdam Neuroscience, Amsterdam, The Netherlands;InflaRx GmbH, Jena, Germany;

关键词: SARS-CoV-2;    COVID-19;    Complement;    Complement inhibition;    Vilobelimab;    C5a;   

DOI  :  10.1186/s12931-022-02278-1

 received in 2022-10-05, accepted in 2022-12-05,  发布年份 2022

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

Fig. 5