Platelet Reactivity and Inflammatory Phenotype Induced by Full-Length Spike SARS-CoV-2 Protein and Its RBD Domain

• Published in: International journal of molecular sciences 2022-12, Vol.23 (23), p.15191
• Main Authors: Cano-Mendez, Alan, García-Larragoiti, Nallely, Damian-Vazquez, Maria, Guzman-Cancino, Patricia, Lopez-Castaneda, Sandra, Ochoa-Zarzosa, Alejandra, Viveros-Sandoval, Martha Eva
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood Platelets - metabolism; CD40 antigen; Collagen; Coronaviruses; COVID-19; COVID-19 - metabolism; Cytokine storm; Flow cytometry; Humans; Inflammation; Interleukin 6; Interleukin 8; P-selectin; Phenotypes; Platelet Activation; Platelet aggregation; Protein Domains; Proteins; RBD domain; SARS-CoV-2; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; spike protein; Thrombocytopenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232315191

A state of immunothrombosis has been reported in COVID-19. Platelets actively participate in this process. However, little is known about the ability of SARS-CoV-2 virus proteins to induce platelet activity. Platelet-rich plasma (PRP) was incubated with spike full-length protein and the RBD domain in independent assays. We evaluated platelet activation through the expression of P-selectin and activation of glicoprotein IIbIIIa (GP IIbIIIa), determined by flow cytometry and the ability of the proteins to induce platelet aggregation. We determined concentrations of immunothrombotic biomarkers in PRP supernatant treated with the proteins. We determined that the spike full-length proteins and the RBD domain induced an increase in P-selectin expression and GP IIbIIIa activation (p < 0.0001). We observed that the proteins did not induce platelet aggregation, but favored a pro-aggregating state that, in response to minimal doses of collagen, could re-establish the process (p < 0.0001). On the other hand, the viral proteins stimulated the release of interleukin 6, interleukin 8, P-selectin and the soluble fraction of CD40 ligand (sCD40L), molecules that favor an inflammatory state p < 0.05. These results indicate that the spike full-length protein and its RBD domain can induce platelet activation favoring an inflammatory phenotype that might contribute to the development of an immunothrombotic state.