COVID-19, Pre-Eclampsia, and Complement System

• Published in: Frontiers in immunology Vol. 12; p. 775168
• Main Authors: Agostinis, Chiara, Mangogna, Alessandro, Balduit, Andrea, Aghamajidi, Azin, Ricci, Giuseppe, Kishore, Uday, Bulla, Roberta
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.11.2021
• Subjects: Complement Inactivator Proteins - therapeutic use; complement system; Complement System Proteins - immunology; COVID-19; COVID-19 - drug therapy; COVID-19 - immunology; COVID-19 - physiopathology; Endothelium - immunology; Female; Humans; Immunology; pre-eclampsia; Pre-Eclampsia - immunology; Pre-Eclampsia - physiopathology; Pre-Eclampsia - prevention & control; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Pregnancy Complications, Infectious - immunology; Pregnancy Complications, Infectious - physiopathology; SARS-CoV-2; Thrombosis - immunology; COVID-19; SARS-CoV-2; pre-eclampsia; complement system; pregnancy
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.775168

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.