Is there an interplay between the SARS-CoV-2 spike protein and Platelet-Activating factor?

Previous publications have reported a potent effect of COVID-19 on platelet function and that the Spike protein enhances washed human platelet aggregation induced by various agonists. This study aims to evaluate whether mRNA vaccination for COVID-19 affects human platelet-rich plasma (hPRP) aggregation response, whether a recombinant Spike protein modulates PAF-induced aggregation in hPRP and in washed rabbit platelets (WRP), and to investigate the effect of recombinant Spike protein on the PAF production in the U-937 cell line. Our results showed that PRP from vaccinated individuals exhibited ex vivo lower EC 50 values in response to PAF, ADP, and collagen. Platelet incubation with the Spike protein alone did not induce aggregation either in hPRP or in WRP, but resulted in augmentation of in vitro PAF-induced aggregation in hPRP from non-vaccinated individuals and in WRP. When PRP from vaccinated individuals was incubated with the Spike protein and PAF was subsequently added, elimination of the secondary wave of the biphasic aggregation curve was recorded compared with the aggregation induced by PAF alone. Collagen-induced in vitro aggregation was dose-dependently reduced when platelets were pre-incubated with the Spike protein in all tested aggregation experiments. Stimulation of U-937 by the Spike protein induced an increase in intracellular PAF production accompanied by elevation of the activities of all three PAF biosynthetic enzymes. In conclusion, since the Spike protein appears to modulate PAF production and activity, the use of compounds that act as PAF inhibitors, could be considered at least in mild cases of patients infected with SARS-CoV-2.