Treatment of COVID-19 With Conestat Alfa, a Regulator of the Complement, Contact Activation and Kallikrein-Kinin System

A dysregulated immune response with hyperinflammation is observed in patients with severe coronavirus disease 2019 (COVID-19). The aim of the present study was to assess the safety and potential benefits of human recombinant C1 esterase inhibitor (conestat alfa), a complement, contact activation and...

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Published in:Frontiers in immunology Vol. 11; p. 2072
Main Authors: Urwyler, Pascal, Moser, Stephan, Charitos, Panteleimon, Heijnen, Ingmar A. F. M., Rudin, Melanie, Sommer, Gregor, Giannetti, Bruno M., Bassetti, Stefano, Sendi, Parham, Trendelenburg, Marten, Osthoff, Michael
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 14.08.2020
Subjects:
Aged
Aged, 80 and over
Betacoronavirus - drug effects
C1 esterase inhibitor
Complement C1 - antagonists & inhibitors
Complement C1 Inhibitor Protein - analysis
Complement C1 Inhibitor Protein - therapeutic use
complement system
Coronavirus Infections - drug therapy
COVID-19
Cytokine Release Syndrome - drug therapy
Factor XIa - antagonists & inhibitors
Female
Humans
Immunology
inflammation
kallikrein-kinin system
Kallikrein-Kinin System - drug effects
Kallikreins - antagonists & inhibitors
Male
Middle Aged
Pandemics
Pneumonia, Viral - drug therapy
Recombinant Proteins - therapeutic use
SARS-CoV-2
Viral Load - drug effects
COVID-19
kallikrein-kinin system
SARS-CoV-2
inflammation
complement system
contact activation system
C1 esterase inhibitor
ISSN:1664-3224, 1664-3224
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Summary:A dysregulated immune response with hyperinflammation is observed in patients with severe coronavirus disease 2019 (COVID-19). The aim of the present study was to assess the safety and potential benefits of human recombinant C1 esterase inhibitor (conestat alfa), a complement, contact activation and kallikrein-kinin system regulator, in severe COVID-19. Patients with evidence of progressive disease after 24 h including an oxygen saturation <93% at rest in ambient air were included at the University Hospital Basel, Switzerland in April 2020. Conestat alfa was administered by intravenous injections of 8400 IU followed by 3 additional doses of 4200 IU in 12-h intervals. Five patients (age range, 53-85 years; one woman) with severe COVID-19 pneumonia (11-39% lung involvement on computed tomography scan of the chest) were treated a median of 1 day (range 1-7 days) after admission. Treatment was well-tolerated. Immediate defervescence occurred, and inflammatory markers and oxygen supplementation decreased or stabilized in 4 patients (e.g., median C-reactive protein 203 (range 31-235) mg/L before vs. 32 (12-72) mg/L on day 5). Only one patient required mechanical ventilation. All patients recovered. C1INH concentrations were elevated before conestat alfa treatment. Levels of complement activation products declined after treatment. Viral loads in nasopharyngeal swabs declined in 4 patients. In this uncontrolled case series, targeting multiple inflammatory cascades by conestat alfa was safe and associated with clinical improvements in the majority of severe COVID-19 patients. Controlled clinical trials are needed to assess its safety and efficacy in preventing disease progression.
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Edited by: Marcin Okrój, Intercollegiate Faculty of Biotechnology of University of Gdaǹsk and Medical University of Gdaǹsk, Poland
Reviewed by: Timothy M. Thomson, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Zoltan Prohaszka, Semmelweis University, Hungary
ORCID: Michael Osthoff orcid.org/0000-0001-5439-957X
This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
These authors have contributed equally to this work
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.02072