Platelets amplify endotheliopathy in COVID-19

• Published in: Science advances Vol. 7; no. 37; p. eabh2434
• Main Authors: Barrett, Tessa J, Cornwell, MacIntosh, Myndzar, Khrystyna, Rolling, Christina C, Xia, Yuhe, Drenkova, Kamelia, Biebuyck, Antoine, Fields, Alexander T, Tawil, Michael, Luttrell-Williams, Elliot, Yuriditsky, Eugene, Smith, Grace, Cotzia, Paolo, Neal, Matthew D, Kornblith, Lucy Z, Pittaluga, Stefania, Rapkiewicz, Amy V, Burgess, Hannah M, Mohr, Ian, Stapleford, Kenneth A, Voora, Deepak, Ruggles, Kelly, Hochman, Judith, Berger, Jeffrey S
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 10.09.2021
• Subjects: Biomedicine and Life Sciences; Cell Biology; Coronavirus; Health and Medicine; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abh2434

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 and 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 / , 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 P2Y 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.