Authors (including presenting author) :
Lai Kang Yiu
Affiliation :
Intensive Care Unit
Queen Elizabeth Hospital
Introduction :
Cerebral venous sinus thrombosis (CVST) is rare complication of COVID-19 infection and mRNA COVID-19 vaccination (1,2). It is a hallmark of vaccine-induced immune thrombotic thrombocytopenia (VITT) complicating the administration of adenovirus-vectored COVID-19 vaccine. (3,4) Angiotensin-converting enzyme 2 (ACE2) and heparan sulfate proteoglycans (HSPGs) are abundantly expressed on brain microvascular endothelial cells (BMECs) (5,6,7). HSPGs is a necessary co-factor for ACE2-mediated entry of SARS-CoV-2. (8) The interaction of the polyanionic, cell surface-associated-HSPGs lining the BMECs and the positively charged SARS-CoV-2 S-protein promote the transformation of the receptor-binding domain of the S-protein from a closed to an open conformation that facilitate ACE2 binding. (9) Thromboinflammation of BMECs may account for CVST after SARS-CoV-2 infection. The release of spike protein in the circulation after mRNA COVID-19 vaccination may interact with the HSPGs and ACE2 on the BMECs to induce thromboinflammation and CVST (10). Platelet activation with the formation of adenovirus-platelet-leukocyte complexes leading to accelerated platelet clearance in the liver are common following adenovirus administration (11). These adenovirus-platelet-leukocyte complexes are taken up by the liver through interaction with membrane-associated HSPGs which acts as a receptor for viral entry. (12) Perhaps the platelet-activating antibodies directed against PF4 in VITT is induced through interaction of SARS-CoV-2 with the PF4 inside the adenovirus-platelet-leukocyte complexes (13) or with HSPGs in the liver through binding with factor IV/X and C4-binding protein. These platelet-activating antibodies against PF4 then in turn attack the HSPGs over the BMEC and induce CVST.
Objectives :
A review on the role of heparin sulfate proteoglycans in the pathogenesis of cerebral venous sinus thrombosis after natural COVID-19 infection, after mRNA COVID-19 vaccination and after adenovirus vectored vaccination.
Methodology :
A review of the literature
Result & Outcome :
This may explain the role of heparin in the management of COVID-19 apart from its anticoagulant action.
