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.
Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland.
Mol Immunol. 2022 Oct;150:99-113. doi: 10.1016/j.molimm.2022.08.008. Epub 2022 Aug 22.
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.
由 SARS-CoV-2 引起的 2019 年冠状病毒病（COVID-19）与从无症状携带者到有并发症的重病患者的临床谱相关，包括血栓栓塞事件、心肌损伤、多系统炎症综合征和死亡。自大流行开始以来，出现了多种治疗选择，大量随机试验改变了 COVID-19 的医学格局。各种单克隆抗体、抗病毒、抗炎和抗凝药物的效果已经过研究，并在一定程度上应用于临床实践。此外，大量试验提高了对疾病的认识，新出现的证据表明补体系统、激肽释放酶-激肽系统和接触激活系统在严重 COVID-19 中作为疾病驱动因素的重要作用。尽管它们与 COVID-19 有关，但针对这些血浆级联的治疗方法既没有得到系统研究，也没有引入临床实践，而且关于这些治疗方法的随机研究也很少。鉴于 C1 抑制剂（C1-INH）作为这些级联的天然抑制剂，具有多作用、多靶点的性质，该药可能是预防疾病进展和对抗 COVID-19 中血栓炎症的一个有趣候选药物。本叙述性综述将讨论这些血浆级联以及内皮细胞在 COVID-19 中的作用的现有证据。此外，我们总结了 C1-INH 在 COVID-19 中的证据以及 C1-INH 在 COVID-19 中的潜在益处和治疗陷阱。
