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While the wild-type (WT) spike protein enhances platelet activity, the effects of the Omicron variant remain unclear. This study compared the effects of WT and Omicron spike proteins on platelet function in 10 healthy participants. We evaluated spike protein binding, P-selectin (platelet activation marker) expression, and aggregability using the Friedman test and Dunn\u2019s post-hoc test. Results showed that both WT and Omicron spike proteins significantly increased binding to platelets and enhanced ADP-induced P-selectin expression compared to the control. However, neither protein significantly affected P-selectin expression under basal conditions or aggregation under low-dose (2 \u00b5M) ADP stimulation. Notably, under SFLLRN stimulation, only the Omicron variant significantly increased aggregation compared to the control, while the WT did not. No significant differences were observed between WT and Omicron across all assays. These findings suggest that the Omicron variant maintains a potent ability to modulate platelet reactivity, particularly through specific signaling pathways, despite numerous mutations. The qualitative nature of the spike protein-platelet interaction may play a crucial role in activation, highlighting the persistent prothrombotic risk across SARS-CoV-2 variants.<\/jats:p>","DOI":"10.1038\/s41598-026-46081-0","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:34:18Z","timestamp":1775759658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 Omicron variant spike protein maintains the ability to bind and activate human platelets: Comparison with the wild-type"],"prefix":"10.1038","volume":"16","author":[{"given":"Eriko","family":"Kusudo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuguhiro","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritoki","family":"Egi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"46081_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/1348-0421.12945","volume":"66","author":"M Takeda","year":"2022","unstructured":"Takeda, M. 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