Research ExplorerPublicationsPlatelets amplify endotheliopathy in COVID-19

Platelets amplify endotheliopathy in COVID-19

Standard

Platelets amplify endotheliopathy in COVID-19. / 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.

In: SCI ADV, Vol. 7, No. 37, 10.09.2021, p. eabh2434.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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 2021, 'Platelets amplify endotheliopathy in COVID-19', SCI ADV, vol. 7, no. 37, pp. eabh2434. https://doi.org/10.1126/sciadv.abh2434

APA

Barrett, T. J., Cornwell, M., Myndzar, K., Rolling, C. C., Xia, Y., Drenkova, K., Biebuyck, A., Fields, A. T., Tawil, M., Luttrell-Williams, E., Yuriditsky, E., Smith, G., Cotzia, P., Neal, M. D., Kornblith, L. Z., Pittaluga, S., Rapkiewicz, A. V., Burgess, H. M., Mohr, I., ... Berger, J. S. (2021). Platelets amplify endotheliopathy in COVID-19. SCI ADV, 7(37), eabh2434. https://doi.org/10.1126/sciadv.abh2434

Vancouver

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. https://doi.org/10.1126/sciadv.abh2434

Bibtex

@article{e0f720776619439a92f5a4538deaa7e1,
title = "Platelets amplify endotheliopathy in COVID-19",
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.",
author = "Barrett, {Tessa J} and MacIntosh Cornwell and Khrystyna Myndzar and Rolling, {Christina C} and Yuhe Xia and Kamelia Drenkova and Antoine Biebuyck and Fields, {Alexander T} and Michael Tawil and Elliot Luttrell-Williams and Eugene Yuriditsky and Grace Smith and Paolo Cotzia and Neal, {Matthew D} and Kornblith, {Lucy Z} and Stefania Pittaluga and Rapkiewicz, {Amy V} and Burgess, {Hannah M} and Ian Mohr and Stapleford, {Kenneth A} and Deepak Voora and Kelly Ruggles and Judith Hochman and Berger, {Jeffrey S}",
year = "2021",
month = sep,
day = "10",
doi = "10.1126/sciadv.abh2434",
language = "English",
volume = "7",
pages = "eabh2434",
journal = "SCI ADV",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "37",

}

RIS

TY - JOUR

T1 - Platelets amplify endotheliopathy in COVID-19

AU - Barrett, Tessa J

AU - Cornwell, MacIntosh

AU - Myndzar, Khrystyna

AU - Rolling, Christina C

AU - Xia, Yuhe

AU - Drenkova, Kamelia

AU - Biebuyck, Antoine

AU - Fields, Alexander T

AU - Tawil, Michael

AU - Luttrell-Williams, Elliot

AU - Yuriditsky, Eugene

AU - Smith, Grace

AU - Cotzia, Paolo

AU - Neal, Matthew D

AU - Kornblith, Lucy Z

AU - Pittaluga, Stefania

AU - Rapkiewicz, Amy V

AU - Burgess, Hannah M

AU - Mohr, Ian

AU - Stapleford, Kenneth A

AU - Voora, Deepak

AU - Ruggles, Kelly

AU - Hochman, Judith

AU - Berger, Jeffrey S

PY - 2021/9/10

Y1 - 2021/9/10

N2 - 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.

AB - 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.

U2 - 10.1126/sciadv.abh2434

DO - 10.1126/sciadv.abh2434

M3 - SCORING: Journal article

C2 - 34516880

VL - 7

SP - eabh2434

JO - SCI ADV

JF - SCI ADV

SN - 2375-2548

IS - 37

ER -