Platelets amplify endotheliopathy in COVID-19
Copyright © 2021 The Authors, some rights reserved; Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified S100A8 and S100A9 as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2. Consistent with increased gene expression, the heterodimer protein product of S100A8/A9, myeloid-related protein (MRP) 8/14, was released to a greater extent by platelets from COVID-19 patients relative to controls. We demonstrate that platelet-derived MRP8/14 activates ECs, promotes an inflammatory hypercoagulable phenotype, and is a significant contributor to poor clinical outcomes in COVID-19 patients. Last, we present evidence that targeting platelet P2Y12 represents a promising candidate to reduce proinflammatory platelet-endothelial interactions. Together, these findings demonstrate a previously unappreciated role for platelets and their activation-induced endotheliopathy in COVID-19.
Barrett, T., Cornwell, M., Myndzar, K., Rolling, C., Xia, Y., Drenkova, K., Biebuyck, A., Fields, A., Tawil, M., Luttrell-Williams, E., Yuriditsky, E., Smith, G., Cotzia, P., Neal, M., Kornblith, L., Pittaluga, S., Rapkiewicz, A., Burgess, H., Mohr, I., Stapleford, K., Voora, D., Ruggles, K., Hochman, J., & Berger, J. (2021). Platelets amplify endotheliopathy in COVID-19. Science Advances, 7 (37). http://dx.doi.org/10.1126/sciadv.abh2434