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The impact of Gam-COVID-Vac, an Adv5/Adv26 COVID-19 vaccine, on the biomarkers of endothelial function, coagulation and platelet activation

Anar Turmukhambetova, Sergey Yegorov, Ilya Korshukov, Valentina Barkhanskaya, Svetlana Kolesnichenko, Dmitriy Klyuyev, Zhibek Zhumadilova, Aruzhan Pralieva, Laylim Absaghit, Ruslan Belyaev, Dmitriy Babenko, Gonzalo H. Hortelano, Matthew S. Miller, Dmitriy Vazenmiller, Irina Kadyrova 

Abstract

COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although overall considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vectored vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve vaccine safety profile. We assessed changes to the biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n = 58) was assayed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose 2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. A role of persistent endothelial activation following COVID-19 vaccination warrants further investigation.

Introduction

COVID-19 vaccination has occasionally been linked to rare yet severe venous and arterial clotting incidents, both with and without a decrease in platelet count [1, 2]. The majority of these thrombotic events have been related to commonly administered adenoviral vector vaccines, namely the ChAdOx1 CoV-19 vaccine AstraZeneca and the University of Oxford), and the Ad26.COV2.S vaccine (Janssen; Johnson & Johnson) [1, 2]. More recently, a 24-year-old woman experienced a fatal instance of vaccine-induced immune thrombocytopenia and thrombosis (VITT) after receiving the Gam-COVID-Vac ("Sputnik-V" by the Gamaleya Research Institute of Epidemiology and Microbiology) vaccine, showing symptoms on the seventh day after her vaccination [3].

Materials and methods

Study setting

The current analysis is a follow-up to an earlier observational prospective study of safety and reactogenicity of Gam-COVID-Vac in Kazakhstan [9]. Venous blood samples were collected from all participants prior to first meal around a similar time in the morning. Due to a limited sample availability, only a subset of samples from the earlier study was analyzed. Briefly, the main study was conducted in Central Kazakhstan, uncovering the exposure to SARS-CoV-2 by spring 2021 [9–11]. Participants were recruited at the Karaganda Medical University in April-May 2021 (ClinicalTrials.gov #NCT04871841) and consisted of asymptomatic adults who had not previously received a COVID-19 vaccine; individuals with respiratory symptoms or a laboratory-confirmed COVID-19 diagnosis within two weeks prior to the study were excluded. Short questionnaires were administered to gather information on participants’ demographic background and recent history of COVID-19 exposure. At follow-up, participants were screened for respiratory symptoms and tested for COVID-19; participants with COVID-19 at follow-up were excluded. Gam-COVID-Vac administration (0.5 ml dose of vaccine injected into the deltoid muscle) followed the national guidelines and was conducted after sample collection [9]. The vaccine consisted of two doses: the first dose contained rAd26, and the second dose contained rAd5which were injected in 21 day interval according Gam-COVID-Vac injection protocol and National Ministry of Healthcare. Each dose contained 1± 0.5 x1011 rAd particles [9].

Results

We analyzed a total of 58 plasma samples paired across three study visits (baseline, post-dose 1 and post-dose 2) that were available from the original clinical trial.

Using the serological evidence of S-IgG and/or S-IgA, participants were classified based on their prior COVID-19 status as previously. Within the current study subset, there were no discernible demographic or biometric variations between the subgroups with or without prior COVID-19 exposure (Table 1). Due to the limited and variable sample availability, fewer samples were available for some of the assays, such as for PAF.

Discussion

Here we studied the impact of Gam-COVID-Vac on endothelial function, coagulation, and platelet activation biomarkers within a three-week period after the first and second vaccine doses. Vaccination significantly increased ET-1 levels after the first dose, and this elevation was sustained after the second dose. Furthermore, post-dose 2 ET-1 elevation was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Consistent with earlier studies [4, 12], no marked alterations to other biomarkers, including PF4 IgG, were seen. To the best of our knowledge, our study is the first to assess thrombosis-associated biomarkers in the context of Gam-COVID-Vac vaccination. The current lack of studies on this aspect of "Sputnik-V" is partly explained by a shortage of data on the vaccine’s safety and performance outside of Russia, where the vaccine originated [13].

Conclusion

Despite its limitations, our study provides preliminary yet crucial observations regarding alterations in biomarkers related to endothelial function, coagulation, and platelet activation associated with the Gam-COVID-Vac vaccination. The efficacy of COVID-19 vaccines in mitigating the pandemic’s spread is incontrovertibly significant. Nonetheless, the association of these vaccines with a rare but severe prothrombotic state necessitates further comprehensive research, particularly concerning the ramifications of sustained endothelial activation induced by the vaccine.

Acknowledgments

We thank all the participants and clinical and laboratory staff, who have been involved in the study.

Citation: Turmukhambetova A, Yegorov S, Korshukov I, Barkhanskaya V, Kolesnichenko S, Klyuyev D, et al. (2023) The impact of Gam-COVID-Vac, an Adv5/Adv26 COVID-19 vaccine, on the biomarkers of endothelial function, coagulation and platelet activation. PLoS ONE 18(10): e0293074. https://doi.org/10.1371/journal.pone.0293074

Editor: Fadi Aljamaan, King Saud University College of Medicine, SAUDI ARABIA

Received: August 14, 2023; Accepted: October 3, 2023; Published: October 18, 2023

Copyright: © 2023 Turmukhambetova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The study was funded by the Ministry of Healthcare of the Republic of Kazakhstan (Program No.BR11065386, URL: https://www.gov.kz/memleket/entities/dsm?lang=en) to AT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0293074#abstract0

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