Platelets amplify endotheliopathy in COVID-19, 2021, Barrett et al.

Platelets amplify endotheliopathy in COVID-19
Tessa J. Barrett, MacIntosh Cornwell, Khrystyna Myndzar, Christina C. Rolling, Yuhe Xia, Kamelia Drenkova1, Antoine Biebuyck, Alexander T. Fields, Michael Tawil, Elliot Luttrell-Williams, Eugene Yuriditsky, Grace Smith, Paolo Cotzia, Matthew D. Neal, Lucy Z. Kornblith, Stefania Pittaluga, Amy V. Rapkiewicz, Hannah M. Burgess, Ian Mohr, Kenneth A. Stapleford, Deepak Voora, Kelly Ruggles, Judith Hochman, Jeffrey S. Berger

Abstract
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.

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