Abstract
Severe acute respiratory syndrome coronavirus 2 is responsible for the current COVID-19 pandemic resulting in an escalating number of cases and fatalities worldwide. Preliminary evidence from these patients, as well as past coronavirus epidemics, indicates that those infected suffer from disproportionate complement activation as well as excessive coagulation, leading to thrombotic complications and poor outcome. In non-coronavirus cohorts, evidence has accumulated of an interaction between the complement and coagulation systems, with one amplifying activation of the other. A pressing question is therefore if COVID-19 associated thrombosis could be caused by overactivation of the complement cascade? In this review, we summarize the literature on thrombotic complications in COVID-19, complement activation in coronavirus infections, and the crosstalk between the complement and coagulation systems. We demonstrate how the complement system is able to activate the coagulation cascade and platelets, inhibit fibrinolysis and stimulate endothelial cells. We also describe how these interactions see clinical relevance in several disorders where overactive complement results in a prothrombotic clinical presentation, and how it could be clinically relevant in COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus (CoV) responsible for the current COVID-19 pandemic
The aim of this study was to review the literature on complement activation following CoV pneumonia, as well as the crosstalk between the complement and coagulation systems
Complement regulates fibrinolysis, with complement cascade inhibitors demonstrating the ability to inhibit plasmin [27], and complement factors able to activate the fibrinolysis inhibitors plasminogen activator inhibitor-1 (PAI-1) and thrombin-activated fibrinolytic inhibitor (TAFI) [8,10,11]. This collectively suggests that increased complement activity leads to increased coagulation cascade activity and platelet aggregation, i.e. a prothrombotic state, which is exemplified by a number of complementopathies where inappropriate activation of the complement pathways result in thrombotic complications that can be reduced using complement-inhibitors
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus (CoV) responsible for the current COVID-19 pandemic. In non-CoV cohorts, there is evidence of interactions between the complement and coagulation systems, resulting in an amplification of their otherwise targeted responses [4,5,14,15,16,17,18,19,20,21,22,23,6,24,25,26,27,28,29,30,7,8,9,10,11,12,13] It is not known whether this process occurs and could explain the thrombotic complications in COVID-19. We summarize the literature on thrombotic complications in COVID-19, complement activation in CoV infections, and the crosstalk between the complement and coagulation system
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