3. Role of Platelets and in COVID-19
Platelets are traditionally known for their role in haemostasis and formation of thrombi. However, they are increasingly being recognised as key effector cells in inflammation, influencing innate and adaptive immune responses.(Senchenkova, Ansari, et al. 2019) Migration of single platelets act as mechano-sensors to collect and bundle bacteria for neutrophil phagocytosis,(Gaertner et al. 2017) although their uncontrolled activation can result in pathogenic thrombosis. Platelets from COVID-19 patients show increased aggregation, adhesion and spreading on fibrinogen and collagen (via upregulation of the MAPK pathway) and increased activity of thromboxane A2(marker of platelet activation).(Manne et al. 2020)
Thrombocytopenia in COVID-19 is common, with meta-analysis demonstrating a link with a 5-fold increased risk of severe disease.(Lippi, Plebani, and Henry 2020) Thrombocytopenia has also been linked with issues of rare blood clotting events which now surround the Oxford/AstraZeneca vaccine (ongoing pharmacovigilance will determine outcome), with seven deaths being reported in the thirty cases being reported in the UK alone (at the time of writing this review, evidence is shifting towards a causal link between the vaccine and rare blood clots).
Elevated D-dimers, fibrinogen, and von Willebrand factor levels are also associated with a higher mortality rate. Autopsies of cardiac and pulmonary tissue from COVID-19 patients have shown the presence of megakaryocytes.(Rapkiewicz et al. 2020) A recent study by Manne et al., using platelet RNA sequencing demonstrated COVID-19 induced significant changes in platelet transcriptome and proteome, and platelet hyperreactivity,(Manne et al. 2020) which may contribute to COVID-19 pathophysiology by increasing platelet homotypic and heterotypic interactions. During infection, platelets became hyperactive indicated through increased surface P-selectin expression and increased formation of circulating platelet-neutrophil aggregates (PNAs) via binding with PSGL-1.(Manne et al. 2020) The generation of PNAs recruit neutrophils to damaged lung capillaries. Thrombotic events in COVID-19 may be attributed to platelets augmenting inflammation through the generation of NETs and procoagulant platelets, increased aggregates (e.g. PNAs), and the release of bioactive substances. A greater understanding of the role that neutrophils and platelets play in thromboinflammation and their involvement in the pathophysiology of COVID-19 is needed for drug discovery focussing on dampening thromboinflammatory processes.