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Here, we investigate how SARS-CoV-2 spike protein causes platelet activation and aggregation. Our three-dimensional ultrastructural analyses showed that invaginated platelet structures, open canalicular system (OCS), expanded upon activation, trapping viral particles in the process. Binding with platelet OCS concealed SAR-CoV-2 spike-coated particles from virion detection in platelet-depleted blood plasma. Both SARS-CoV-2 spike coated-particles and recombinant spikes specifically induced platelet aggregation with nanoscale filipodia extensions, with the terminal sialic acids of the SARS-CoV-2 spike protein-associated sialoglycoconjugates being the key determinant in platelet activation. Our work illustrates that virus-associated sialic acids, not proteins, are functionally responsible for SARS-CoV-2 induced thrombotic events, providing a mechanistic insight on how glycosylation contributes to disease severity in COVID-19. This study lays the foundation for the development of glycan-modified vaccines with reduced risks of thrombosis.<\/jats:p>","DOI":"10.64898\/2026.04.19.719510","type":"posted-content","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:05:21Z","timestamp":1776744321000},"source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 spike protein-associated sialoglycoconjugates induce nanoscale filipodia to facilitate micro-size platelet clotting"],"prefix":"10.64898","author":[{"given":"Ablikim","family":"Baqi","sequence":"first","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainur","family":"Sanaubarova","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda L","family":"Spillings","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Bremaud","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Masic","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Dirr","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"von Itzstein","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5229-5707","authenticated-orcid":false,"given":"Johnson","family":"Mak","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine & Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042511300844000_2026.04.19.719510v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30937-5"},{"key":"2026042511300844000_2026.04.19.719510v2.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432"},{"key":"2026042511300844000_2026.04.19.719510v2.3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.060785"},{"key":"2026042511300844000_2026.04.19.719510v2.4","doi-asserted-by":"publisher","DOI":"10.7326\/M20-2003"},{"key":"2026042511300844000_2026.04.19.719510v2.5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.3786"},{"key":"2026042511300844000_2026.04.19.719510v2.6","first-page":"1317","article-title":"Platelet gene expression and function in patients with COVID-19. 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