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.