An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy

Abstract

Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Recent studies have revealed that SARS-CoV-2 infection is associated with the generation of thrombosis and coagulopathy. Fundamentally, it has been believed that a diverse array of signalling pathways might be responsible for the activation of coagulation cascade during SARS-CoV-2 infection. Henceforth, a detailed understanding of these probable underlying molecular mechanistic pathways causing thrombosis in Covid-19 disease deserves an urgent exploration. Therefore, in this review, the hypothetical crosstalk between distinct signalling pathways including apoptosis, inflammation, hypoxia and angiogenesis attributable for the commencement of thrombotic events during SARS-CoV-2 infection has been addressed which might further unravel promising therapeutic targets in Covid-19 disease.

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

“…The cytokine storm is characterized by high serum levels of various cytokine mixtures, such as IL-1β, IL-6, IL-7, IL-8, IL-9, IL-10, IL-18, IL-33, FGF (fibroblast growth factor), G-CSF (granulocyte-colony stimulating Factor), GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN-γ (interferon-γ), CCL-2 (CC-chemokine ligand 2), IP-10 (interferon-gamma induced protein 10), MCP-1, MIP-1β (Macrophage Inflammatory Protein 1β), PDGF (platelet-derived growth factor), TNF-α, and VEGF [ 181 , 182 ]. These mixed cytokine stews are pro-coagulatory in nature and induce multiple pathways associated with fibrin generations, including platelet activation and aggregation, activation of coagulation factors and complement components, renin-angiotensin system and tissue-resident macrophages [ 183 , 184 ]. In particular, proinflammatory cytokines, IL-1ß, IL-6, IL-8 and TNF-α, resulted in platelet hyperactivation with increased clumps, suggesting that these molecules possess profound effect on rumpled fibrin clot with trapped RBCs [ 185 , 186 ].…”

MicroRNA 205-5p and COVID-19 adverse outcomes: Potential molecular biomarker and regulator of the immune response

“…This induction of VEGFA tissue expression was attributed mainly to the cytokine storm process and to the COVID-19-related hypoxia state, which can induce a pro-angiogenic response. However, this angiogenic stimulus appears to be responsible for an increase of endothelial lung cell permeability that further impairs endothelium function and triggers tissue factor (TF) release, which leads to the establishment of a pro-thrombotic environment, [35][36][37][38] once this interaction, in theory, could minimize the angiogenesis process and avoid organ damage. Thus, considering that our results showed that miR-205-5p is present in the serum of patients who presented non-fatal and fatal COVID-19, but significantly upregulated in the last cohort, we hypothesize that miR-205-5p could be involved in the COVID-19 pathophysiology both as an inducer of inflammation and as a cell regulator released in response to VEGFA over-expression.…”

A case of aseptic bilateral cavernous sinus thrombosis following a recent inactivated SARS-CoV-2 vaccination

“…The interaction between the virus and the ACE-2 receptors yields an imbalanced shift, inducing inflammation, vasoconstriction, and coagulation cascade. [ 4 ]…”