C1 Esterase Inhibition: Targeting Multiple Systems in COVID-19
niet 1 maar meerdere, hou dit in je achterhoofd
Numerous medications involved in C1-INH pathways are clinically available for the treatment of hereditary angioedema (HAE), which is caused by deficient or dysfunctional C1-INH (Fig. 1b) [6, 7]. COVID-19 and HAE share clinical overlap with symptoms such as shortness of breath, diarrhea, abdominal pain, and facial swelling [8]. In HAE, increased vascular permeability results in angioedema that can manifest as facial and extremity swelling or mucosal edema of the respiratory and gastrointestinal tracts. It has been hypothesized that the dry cough, ground-glass lung opacities, and sensitivity to fluid overload in COVID-19 may be related to pulmonary angioedema [9,10,11]. Mechanistically, COVID-19 and HAE share innate immune activation that results in inflammation, endothelial dysfunction, and fibrinolysis. In the terminal complement cascade, dysregulation can result in thrombotic microangiopathy
characterized by thrombosis and organ injury, a common finding in COVID-19 [1]. The terminal complement cascade can be initiated by the classical pathway via the C1 complex, the alternative pathway, and the lectin pathway.