Alterations in platelets during SARS-CoV-2 infection

Abstract

Coronavirus disease 2019 (COVID-19) is a pandemic syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection induces a process of inflammation and thrombosis supported by an altered platelet activation state. This platelet activation is peculiar being characterized by the formation of platelet-leukocytes rather than platelet-platelet aggregates and by an increased procoagulant potential supported by elevated levels of TF positive platelets and microvesicles.Therapeutic strategies targeting, beyond systemic inflammation (i.e. with tocilizumab, an anti interleukin-6 receptor), this state of platelet activation might therefore be beneficial. Among the antithrombotic drugs proposed as candidates to treat patients with SARS-CoV-2 infection, antiplatelet drugs, such as aspirin are showing promising results.

Keywords: Antiplatelet drugs; COVID-19; coagulation; platelets; thrombosis.

Figure 1.

Platelet alterations in COVID-19 disease. As the SARS-Cov-2 infection progresses, the uncontrolled overproduction of inflammatory cytokines (1) may contribute to platelet activation resulting in increased exposure of P-selectin and Tissue Factor on the surface of circulating platelets.Platelet hyperreactivity may also be a consequence of the effect of SARS-CoV-2 on megakaryocytes. This results in the production of activated platelets characterized by significant changes in their transcriptome (2). Diabetes or cardiovascular diseases, characterized di per se by a sustained platelet activation state, may determine the presence in circulation of COVID-19 patients, of “primed platelets” more prone to activation (3). In addition, the altered platelet activation can be a direct consequence of the virus activity that, once internalized, can determine a Toll like receptor 7-mediated release of platelet granules (4). Finally, activation of endothelial cells, which is another hallmarks of COVID-19 disease, may result in a NO pathway dysfunction (5) that can promote and sustain further platelet activation. These mechanisms, which are not reciprocally exclusive, are responsible for (a) an increase in circulating procoagulant platelets expressing Tissue Factor, which are therefore able to support thrombin generation, and P-selectin-positive platelets available for the formation of heteroaggregates with monocytes and neutrophils (b). The release of alpha and dense granule cargo as well as the production of extracellular vesicles are further consequences of platelet activation (c,d). The interaction between platelets and neutrophils causes the formation of highly prothrombotic NETs (e) that can support the formation of fibrin-rich microthrombi that have been shown in the lung of COVID-19 patients (f,g)