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Molecular immunology
10, 2022;150 99-113.

Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.

Pascal Urwyler, Stephan Moser, Marten Trendelenburg, Parham Sendi, Michael Osthoff
Author Information
  1. Pascal Urwyler: Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland.
  2. Stephan Moser: Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland.
  3. Marten Trendelenburg: Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
  4. Parham Sendi: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
  5. Michael Osthoff: Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland. Electronic address: michael.osthoff@usb.ch.
PMID: 36030710 DOI: 10.1016/j.molimm.2022.08.008

Abstract

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is associated with a clinical spectrum ranging from asymptomatic carriers to critically ill patients with complications including thromboembolic events, myocardial injury, multisystemic inflammatory syndromes and death. Since the beginning of the pandemic several therapeutic options emerged, with a multitude of randomized trials, changing the medical landscape of COVID-19. The effect of various monoclonal antibodies, antiviral, anti-inflammatory and anticoagulation drugs have been studied, and to some extent, implemented into clinical practice. In addition, a multitude of trials improved the understanding of the disease and emerging evidence points towards a significant role of the complement system, kallikrein-kinin, and contact activation system as drivers of disease in severe COVID-19. Despite their involvement in COVID-19, treatments targeting these plasmatic cascades have neither been systematically studied nor introduced into clinical practice, and randomized studies with regards to these treatments are scarce. Given the multiple-action, multiple-target nature of C1 inhibitor (C1-INH), the natural inhibitor of these cascades, this drug may be an interesting candidate to prevent disease progression and combat thromboinflammation in COVID-19. This narrative review will discuss the current evidence with regards to the involvement of these plasmatic cascades as well as endothelial cells in COVID-19. Furthermore, we summarize the evidence of C1-INH in COVID-19 and potential benefits and pitfalls of C1-INH treatment in COVID-19.

Keywords

C1 inhibitor COVID-19 Complement system Contact activation system Kallikrein-kinin system Thromboinflammation

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MeSH Term

Antibodies, Monoclonal
Anticoagulants
Antiviral Agents
Complement C1 Inhibitor Protein
Disease Progression
Endothelial Cells
Humans
Inflammation
Kallikreins
Kinins
SARS-CoV-2
Thromboinflammation
Thrombosis
COVID-19 Drug Treatment

Chemicals

Antibodies, Monoclonal
Anticoagulants
Antiviral Agents
Complement C1 Inhibitor Protein
Kinins
Kallikreins
Journal Article Review Research Support, Non-U.S. Gov't

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