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Platelets amplify endotheliopathy in COVID-19.

Publication ,  Journal Article
Barrett, TJ; Cornwell, M; Myndzar, K; Rolling, CC; Xia, Y; Drenkova, K; Biebuyck, A; Fields, AT; Tawil, M; Luttrell-Williams, E; Yuriditsky, E ...
Published in: Sci Adv
September 10, 2021

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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Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

September 10, 2021

Volume

7

Issue

37

Start / End Page

eabh2434

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Barrett, T. J., Cornwell, M., Myndzar, K., Rolling, C. C., Xia, Y., Drenkova, K., … Berger, J. S. (2021). Platelets amplify endotheliopathy in COVID-19. Sci Adv, 7(37), eabh2434. https://doi.org/10.1126/sciadv.abh2434
Barrett, Tessa J., MacIntosh Cornwell, Khrystyna Myndzar, Christina C. Rolling, Yuhe Xia, Kamelia Drenkova, Antoine Biebuyck, et al. “Platelets amplify endotheliopathy in COVID-19.Sci Adv 7, no. 37 (September 10, 2021): eabh2434. https://doi.org/10.1126/sciadv.abh2434.
Barrett TJ, Cornwell M, Myndzar K, Rolling CC, Xia Y, Drenkova K, et al. Platelets amplify endotheliopathy in COVID-19. Sci Adv. 2021 Sep 10;7(37):eabh2434.
Barrett, Tessa J., et al. “Platelets amplify endotheliopathy in COVID-19.Sci Adv, vol. 7, no. 37, Sept. 2021, p. eabh2434. Pubmed, doi:10.1126/sciadv.abh2434.
Barrett TJ, Cornwell M, Myndzar K, Rolling CC, Xia Y, Drenkova K, Biebuyck A, Fields AT, Tawil M, Luttrell-Williams E, Yuriditsky E, Smith G, Cotzia P, Neal MD, Kornblith LZ, Pittaluga S, Rapkiewicz AV, Burgess HM, Mohr I, Stapleford KA, Voora D, Ruggles K, Hochman J, Berger JS. Platelets amplify endotheliopathy in COVID-19. Sci Adv. 2021 Sep 10;7(37):eabh2434.

Published In

Sci Adv

DOI

EISSN

2375-2548

Publication Date

September 10, 2021

Volume

7

Issue

37

Start / End Page

eabh2434

Location

United States