Prothrombotic events are prominent hallmarks of a severe Covid-19 infection. Although
the exact mechanisms underlying these thromboinflammations are still unclear, evidence
suggests that platelets play a crucial role. Studies have shown that platelets from
Covid-19 patients are hyperactivated, leading to the formation of microthrombi and
providing a higher risk of mortality. Hence, we investigated the impact of spike-coated
beads on platelets to find a major mechanism, leading to platelet hyperactivation.
Activation of platelets was investigated after coincubation of washed platelets from
healthy donors and spike-coated beads. Aggregation and activation were measured by
the use of aggregometry and FACS staining of activation markers. Stimulation of platelets
with spike-beads induced platelet aggregation and expression of activation markers.
This activation process required the presence of plasma, pointing to the contribution
of soluble factors. Considering that immune complexes are able to activate platelets,
we assessed their contribution to spike-beads-induced platelet activation. Indeed,
spike-beads can bind IgG in plasma from vaccinated donors. Using a blocking antibody
for the FcγRIIa receptor, we were able to inhibit platelet aggregation by spike-beads,
suggesting that the activation occurs through stimulation of the low-affinity receptor
for IgG. Taking into account, that prothrombotic events are induced by multiple factors,
it is important to elucidate this process in detail to understand the pathobiology.
Here, we describe a powerful model, which is useful to dissect multifactorial-induced
thrombotic events. Overall, this study provides a possible mechanism of platelet activation
in a SARS-CoV-2 infection, which opens new avenues for therapeutic options.
