Platelet polyphosphate and SARS-Cov-2 mRNA-vaccine-induced inflammatory side effects: a pilot study
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Abstract
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
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The COVID-19 mRNA vaccines (BNT162b2) reduced platelet polyP levels after the initial dose, but not after the 2 nd dose, in relatively younger female subjects.
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Relatively older male subjects did not respond to the vaccination by reducing platelet polyP.
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These findings suggest that platelets release polyP to suppress vaccine-induced reactions, for example, inflammation, which is usually recognized as a side effect.
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However, such suppression could be observed in subjects with higher immune responses, generally in relatively younger female subjects.
Article activity feed
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SciScore for 10.1101/2021.09.13.21263437: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study design and consent forms for all procedures (project identification code: 2019–0423) were approved by the Ethics Committee for Human Participants at the Niigata University School of Medicine (Niigata, Japan) and complied with the Helsinki Declaration of 1964, as revised in 2013. 2.2 Fluorometric measurement of platelet polyphosphate using DAPI: After storage at 4 °C for 24 h, the fixed platelets were centrifuged at 578 × g for 5 min, and the supernatants were carefully aspirated as much as possible. Sex as a biological variable The female groups (initial dose=36.3±15.0, second dose=36.3±12.3) were significantly younger in average than the male groups (initial dose=56.8±8.8, … SciScore for 10.1101/2021.09.13.21263437: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study design and consent forms for all procedures (project identification code: 2019–0423) were approved by the Ethics Committee for Human Participants at the Niigata University School of Medicine (Niigata, Japan) and complied with the Helsinki Declaration of 1964, as revised in 2013. 2.2 Fluorometric measurement of platelet polyphosphate using DAPI: After storage at 4 °C for 24 h, the fixed platelets were centrifuged at 578 × g for 5 min, and the supernatants were carefully aspirated as much as possible. Sex as a biological variable The female groups (initial dose=36.3±15.0, second dose=36.3±12.3) were significantly younger in average than the male groups (initial dose=56.8±8.8, second dose=56.0±7.8) in both cases. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources The Mann-Whitney U test was performed to compare the two groups (SigmaPlot 13.0; Systat Software, Inc., San Jose, CA, USA). SigmaPlotsuggested: (SigmaPlot, RRID:SCR_003210)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:4.5 Limitations: In Japan, the vaccination of medical staff is strictly controlled and scheduled. In addition, our limited capacity to handle samples made it difficult to secure sufficient donor numbers. As a result, we could not expand the sample size to what we originally calculated. Thus, further investigation is needed to reach a definitive conclusion; however, the present findings regarding gender and age differences seem to essentially be consistent with the previous reports of antibody formation36-38 and, as a pilot study, are worth further investigation.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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