Platelet polyphosphate and SARS-Cov-2 mRNA-vaccine-induced inflammatory side effects: a pilot study

Background

Platelets have recently been recognized as immune cells. Platelets first contact invading pathogens and then induce immune reactions in cooperation with white blood cells. Platelet polyphosphate (polyP), which is classically recognized as a thrombotic and hemostatic biomolecule, has recently attracted attention as a ‘cytokine’ that modulates inflammation and is involved in intercellular communication between platelets and major immune cells.

Objective

To determine the involvement of polyP in SARS-Cov-2-mRNA vaccine-induced immune responses, this pilot study examined the effects of mRNA vaccines on platelet polyP levels.

Methods

Before and after vaccination (BNT162b2), blood samples were obtained from healthy, non-smoking individuals (relatively older male group, n=6 vs. younger female group, n=23), who did not have systemic diseases that required continuous treatment. Washed platelets were prepared and subjected to a fluorometric determination of platelet polyP levels using 4’,6-diamidino-2-phenylindole. The side effects of vaccination were recorded as scores.

Results

Compared with the male group, platelet polyP levels decreased in the relatively younger female group after the initial dose, while the side effect score increased in the female group after the second dose. Moderate correlation coefficients were observed between the reduction in polyP levels and the side effect scores or the original polyP levels.

Conclusions

Despite being a pilot study using a small sample size, this study suggests the possibility that platelet polyP may suppress the side effects induced by the mRNA vaccines after the initial dose, but not the second dose, in relatively young female subjects who generally have high immune responsiveness.

Essentials

• The COVID-19 mRNA vaccines (BNT162b2) reduced platelet polyP levels after the initial dose, but not after the 2^nddose, in relatively younger female subjects.

• Relatively older male subjects did not respond to the vaccination by reducing platelet polyP.

• These findings suggest that platelets release polyP to suppress vaccine-induced reactions, for example, inflammation, which is usually recognized as a side effect.

• However, such suppression could be observed in subjects with higher immune responses, generally in relatively younger female subjects.