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.
Competing Interests: Conflict of interest Dr. Trendelenburg reports receiving grants from the Swiss National Science Foundation, Roche, Novartis, and Idorsia outside of the submitted work. Dr. Osthoff reports receiving grants from the Swiss National Science Foundation and Pharming Technologies B.V. for the investigator-initiated trial of rhC1INH in COVID-19 (ClinicalTrials.gov Identifier: NCT04414631), and from the Botnar Research Centre for Child Health outside the submitted work, and consulting fees from Pharming Technologies B.V. No other disclosures or conflicting interests with regards to this work have been reported.
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