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

doi:10.1007/s11239-023-02891-x

. 2023 Nov;56(4):538-547.

doi: 10.1007/s11239-023-02891-x. Epub 2023 Sep 22.

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

Ziv Sevilya¹, Alona Kuzmina², Michal Cipok³, Vera Hershkovitz³, Danielle Keidar-Friedman⁴, Ran Taube², Eli I Lev^{5

6}

Affiliations

¹ Cardiology Department, Assuta Ashdod Medical Center, Ashdod, Israel. zivse@assuta.co.il.
² The Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
³ Hematology Laboratory, Assuta Ashdod Medical Center, Ashdod, Israel.
⁴ Laboratory Division, Assuta Ashdod Medical Center, Ashdod, Israel.
⁵ Cardiology Department, Assuta Ashdod Medical Center, Ashdod, Israel.
⁶ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

PMID: 37736784
DOI: 10.1007/s11239-023-02891-x

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

Ziv Sevilya et al. J Thromb Thrombolysis. 2023 Nov.

. 2023 Nov;56(4):538-547.

doi: 10.1007/s11239-023-02891-x. Epub 2023 Sep 22.

Authors

Ziv Sevilya¹, Alona Kuzmina², Michal Cipok³, Vera Hershkovitz³, Danielle Keidar-Friedman⁴, Ran Taube², Eli I Lev^{5

6}

Affiliations

¹ Cardiology Department, Assuta Ashdod Medical Center, Ashdod, Israel. zivse@assuta.co.il.
² The Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
³ Hematology Laboratory, Assuta Ashdod Medical Center, Ashdod, Israel.
⁴ Laboratory Division, Assuta Ashdod Medical Center, Ashdod, Israel.
⁵ Cardiology Department, Assuta Ashdod Medical Center, Ashdod, Israel.
⁶ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

PMID: 37736784
DOI: 10.1007/s11239-023-02891-x

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.

Keywords: Delta variant; Platelets activation; SARS-CoV-2; SARS-CoV-2 variants; Thrombosis.

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[1] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for Covid-19 (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382(18):1708–1720. https://doi.org/10.1056/NEJMoa2002032 - DOI - PubMed

[2] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for Covid-19 (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382(18):1708–1720. https://doi.org/10.1056/NEJMoa2002032 - DOI - PubMed

[3] Nahum J, Morichau-Beauchant T, Daviaud F, Echegut P, Fichet J, Maillet JM, Thierry S (2020) Venous thrombosis among critically ill patients with coronavirus disease 2019 (COVID-19). JAMA 3(5):e2010478. https://doi.org/10.1001/jamanetworkopen.2020.10478 - DOI

[4] Nahum J, Morichau-Beauchant T, Daviaud F, Echegut P, Fichet J, Maillet JM, Thierry S (2020) Venous thrombosis among critically ill patients with coronavirus disease 2019 (COVID-19). JAMA 3(5):e2010478. https://doi.org/10.1001/jamanetworkopen.2020.10478 - DOI

[5] Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, Muenchhoff M, Hellmuth JC, Ledderose S, Schulz H, Scherer C, Rudelius M, Zoller M, Höchter D, Keppler O, Teupser D, Zwißler B, von Bergwelt-Baildon M, Kääb S, Massberg S, Pekayvaz K, Stark K (2020) Immunothrombotic dysregulation in COVID-19 Pneumonia is associated with respiratory failure and coagulopathy. Circulation 142(12):1176–1189. https://doi.org/10.1161/CIRCULATIONAHA.120.048488 - DOI - PubMed - PMC

[6] Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, Muenchhoff M, Hellmuth JC, Ledderose S, Schulz H, Scherer C, Rudelius M, Zoller M, Höchter D, Keppler O, Teupser D, Zwißler B, von Bergwelt-Baildon M, Kääb S, Massberg S, Pekayvaz K, Stark K (2020) Immunothrombotic dysregulation in COVID-19 Pneumonia is associated with respiratory failure and coagulopathy. Circulation 142(12):1176–1189. https://doi.org/10.1161/CIRCULATIONAHA.120.048488 - DOI - PubMed - PMC

[7] Conway EM, Mackman N, Warren RQ, Wolberg AS, Mosnier LO, Campbell RA, Gralinski LE, Rondina MT, van de Veerdonk FL, Hoffmeister KM, Griffin JH, Nugent D, Moon K, Morrissey JH (2022) Understanding COVID-19-associated coagulopathy. Nat Rev Immunol 22(10):639–649. https://doi.org/10.1038/s41577-022-00762-9 - DOI - PubMed - PMC

[8] Conway EM, Mackman N, Warren RQ, Wolberg AS, Mosnier LO, Campbell RA, Gralinski LE, Rondina MT, van de Veerdonk FL, Hoffmeister KM, Griffin JH, Nugent D, Moon K, Morrissey JH (2022) Understanding COVID-19-associated coagulopathy. Nat Rev Immunol 22(10):639–649. https://doi.org/10.1038/s41577-022-00762-9 - DOI - PubMed - PMC

[9] Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, Ibrahim H, Friedman GH, Thompson C, Alviar CL, Chadow HL, Fishman GI, Reynolds HR, Keller N, Hochman JS (2020) ST-segment elevation in patients with Covid-19—a case series. N Engl J Med 382(25):2478–2480. https://doi.org/10.1056/NEJMc2009020 - DOI - PubMed

[10] Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, Ibrahim H, Friedman GH, Thompson C, Alviar CL, Chadow HL, Fishman GI, Reynolds HR, Keller N, Hochman JS (2020) ST-segment elevation in patients with Covid-19—a case series. N Engl J Med 382(25):2478–2480. https://doi.org/10.1056/NEJMc2009020 - DOI - PubMed

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

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

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