Platelets amplify endotheliopathy in COVID-19

Authors

Tessa J. Barrett, NYU Grossman School of Medicine
MacIntosh Cornwell, NYU Grossman School of Medicine
Khrystyna Myndzar, NYU Grossman School of Medicine
Christina C. Rolling, NYU Grossman School of Medicine
Yuhe Xia, NYU Grossman School of Medicine
Kamelia Drenkova, NYU Grossman School of Medicine
Antoine Biebuyck, NYU Grossman School of Medicine
Alexander T. Fields, University of California, San Francisco
Michael Tawil, NYU Grossman School of Medicine
Elliot Luttrell-Williams, NYU Grossman School of Medicine
Eugene Yuriditsky, NYU Grossman School of Medicine
Grace Smith, National Cancer Institute (NCI)
Paolo Cotzia, NYU Grossman School of Medicine
Matthew D. Neal, University of Pittsburgh Medical Center
Lucy Z. Kornblith, University of California, San Francisco
Stefania Pittaluga, University of California, San Francisco
Amy V. Rapkiewicz, NYU Langone Health
Hannah M. Burgess, NYU Langone Health
Ian Mohr, NYU Langone Health
Kenneth A. Stapleford, NYU Langone Health
Deepak Voora, Duke University School of Medicine
Kelly Ruggles, NYU Grossman School of Medicine
Judith Hochman, NYU Grossman School of Medicine
Jeffrey S. Berger, NYU Grossman School of Medicine

Document Type

Journal Article

Publication Date

9-1-2021

Journal

Science Advances

Volume

7

Issue

37

DOI

10.1126/sciadv.abh2434

Abstract

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.

APA Citation

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