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Differential platelet activation through an interaction with spike proteins of different SARS-CoV-2 variants

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Abstract

COVID-19 disease is associated with an increased risk of thrombotic complications, which contribute to high short-term mortality. Patients with COVID-19 demonstrate enhanced platelet turnover and reactivity, which may have a role in the development of thrombotic events and disease severity. Evidence has suggested direct interaction between SARS-CoV-2 and platelets, resulting in platelets activation. Here, we compare the effect of various SARS-CoV-2 spike variants on platelet activation. Engineered lentiviral particles were pseudotyped with spike SARS-CoV-2 variants and incubated with Platelet Rich Plasma obtained from healthy individuals. The pseudotyped SARS-CoV-2 exhibiting the wild-type Wuhan-Hu spike protein stimulated platelets to increase expression of the surface CD62P and activated αIIbβ3 markers by 3.5 ± 1.2 and 3.3 ± 0.7 fold, respectively (P = 0.004 and 0.003). The Delta variant induced much higher levels of platelet activation; CD62P expression was increased by 6.6 ± 2.2 fold and activated αIIbβ3 expression was increased by 5.0 ± 1.5 fold (P = 0.005 and 0.026, respectively). The Omicron BA.1 and the Alpha variants induced the lowest level of activation; CD62P expression was increased by 1.7 ± 0.4 and 1.6 ± 0.9 fold, respectively (P = 0.003 and 0.008), and activated αIIbβ3 expression by 1.8 ± 1.1 and 1.6 ± 0.8, respectively (P = 0.003 and 0.001). The Omicron BA.2 variant induced an increase of platelets activation comparable to the Wuhan-Hu (2.8 ± 1.2 and 2.1 ± 1.3 fold for CD62P and activated αIIbβ3 markers, respectively). The results obtained for various COVID-19 variants are in correlation with the clinical severity and mortality reported for these variants.

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Authors and Affiliations

  1. Cardiology Department, Assuta Ashdod Medical Center, Ashdod, Israel

    Ziv Sevilya & Eli I. Lev

  2. The Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Alona Kuzmina & Ran Taube

  3. Hematology Laboratory, Assuta Ashdod Medical Center, Ashdod, Israel

    Michal Cipok & Vera Hershkovitz

  4. Laboratory Division, Assuta Ashdod Medical Center, Ashdod, Israel

    Danielle Keidar-Friedman

  5. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Eli I. Lev

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  1. Ziv Sevilya
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  2. Alona Kuzmina
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  3. Michal Cipok
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  4. Vera Hershkovitz
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  5. Danielle Keidar-Friedman
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  6. Ran Taube
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  7. Eli I. Lev
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Corresponding author

Correspondence to Ziv Sevilya.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles off the Declaration of Helsinki. Approval was granted by the Ethics Committee of Assuta Ashdod medical center.

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Informed consent was obtained from all individuals participants included in the study.

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Sevilya, Z., Kuzmina, A., Cipok, M. et al. Differential platelet activation through an interaction with spike proteins of different SARS-CoV-2 variants. J Thromb Thrombolysis 56, 538–547 (2023). https://doi.org/10.1007/s11239-023-02891-x

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  • DOI: https://doi.org/10.1007/s11239-023-02891-x

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