Platelets amplify endotheliopathy in COVID-19.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • September 10, 2021

Published In

Volume / Issue

  • 7 / 37

Start / End Page

  • eabh2434 -

PubMed ID

  • 34516880

Pubmed Central ID

  • PMC8442885

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abh2434


  • eng

Conference Location

  • United States