Tessa J Barrett, MacIntosh Cornwell, Khrystyna Myndzar, Christina C Rolling, Yuhe Xia, Kamelia Drenkova, 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
Author Information
Tessa J Barrett: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
MacIntosh Cornwell: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Khrystyna Myndzar: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Christina C Rolling: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Yuhe Xia: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Kamelia Drenkova: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Antoine Biebuyck: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Alexander T Fields: Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Michael Tawil: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Elliot Luttrell-Williams: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Eugene Yuriditsky: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Grace Smith: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ORCID
Paolo Cotzia: Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA.
Matthew D Neal: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA. ORCID
Lucy Z Kornblith: Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. ORCID
Stefania Pittaluga: Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. ORCID
Amy V Rapkiewicz: Department of Pathology, NYU Langone Long Island Hospital, New York University Langone Health, Mineola, NY, USA. ORCID
Hannah M Burgess: Department of Microbiology, New York University Langone Health, New York, NY, USA. ORCID
Ian Mohr: Department of Microbiology, New York University Langone Health, New York, NY, USA.
Kenneth A Stapleford: Department of Microbiology, New York University Langone Health, New York, NY, USA.
Deepak Voora: Department of Medicine, Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC, USA.
Kelly Ruggles: Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Judith Hochman: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
Jeffrey S Berger: Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. ORCID
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 and 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 /, 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 P2Y 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.
