Abstract
COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.
Highlights
The first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, responsible for the coronavirus disease 2019 (COVID-19) outbreak, was reported in the Chinese town of Wuhan in the late 2019 [1]
Among the different receptors identified as cellular entry mediators, the main target receptor of the SARS-CoV-2 virus is the angiotensin-converting enzyme 2 (ACE2) [7], which plays an important role in the renin-angiotensin-aldosterone system (RAAS) for the regulation of blood pressure and electrolyte homeostasis [8], and is widely expressed by most tissues, accounting for the high tropism of the virus
The interplay between thrombosis and inflammation is ensured by PAR1 cleavage, upon thrombin-PAR1 interaction, resulting into an overall pro-inflammatory state characterized by the release of P-selectin, von Willebrand factor and the disruption of the endothelial barrier function [88]
Summary
Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus.
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