ABSTRACT
BACKGROUND: Thrombosis plays an important role in the Coronavrus Disease 2019 (COVID-19) infection-related complications such as acute respiratory distress syndrome and myocardial infarction. Multiple factors such as oxygen demand injuries, endothelial cells injury related to infection, and plaque formation. MAIN BODY: Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases. Platelets contain multiple receptors that interact with specific ligands. Pathogen's receptors such as Toll-like receptors (TLRs), NOD-like receptor, C-type lectin receptor family, glycoprotein (GP) such as GPαIIbß3 and GPIbα which allow pathogens to interact with platelets. Platelet TLRs and NOD2 are involved in platelet activation and thrombosis. Accordingly, TLRs are critical receptors that could recognize various endogenous damage-associated molecular patterns and exogenous pathogen-associated molecular patterns (PAMPs). TLRs are considered as important components in the activation of innate immunity response against pathogenic and non-pathogenic components like damaged tissues. TLRs-1,-2,-4,-6,-7 expression on or within platelets has been reported previously. Various PAMPs were indicated to be capable of binding to platelet-TLRs and inducing both the activation and promotion of downstream proinflammatory signaling cascade. CONCLUSION: It is possible that the increased TLRs expression and TLR-mediated platelets activation during COVID-19 may enhance vascular and coronary thrombosis. It may be hypothesized using TLRs antagonist and monoclonal antibody against P-selectin, as the marker of leukocyte recruitment and platelet activation, besides viral therapy provide therapeutic advances in fighting against the thrombosis related complications in COVID-19.
ABSTRACT
Among the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1ß, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.