Platelets contribute to disease severity in COVID-19.
Tessa J Barrett, Seda Bilaloglu, Macintosh Cornwell, Hannah M Burgess, Vitor W Virginio, Kamelia Drenkova, Homam Ibrahim, Eugene Yuriditsky, Yin Aphinyanaphongs, Mark Lifshitz, Feng Xia Liang, Julie Alejo, Grace Smith, Stefania Pittaluga, Amy V Rapkiewicz, Jun Wang, Camelia Iancu-Rubin, Ian Mohr, Kelly Ruggles, Kenneth A Stapleford, Judith Hochman, Jeffrey S Berger
Author Information
Tessa J Barrett: Department of Medicine, New York University Langone Health, New York, New York, USA. ORCID
Seda Bilaloglu: Department of Population Health, New York University Langone Health, New York, New York, USA.
Macintosh Cornwell: Department of Medicine, New York University Langone Health, New York, New York, USA.
Hannah M Burgess: Department of Microbiology, New York University Langone Health, New York, New York, USA.
Vitor W Virginio: Department of Medicine, New York University Langone Health, New York, New York, USA.
Kamelia Drenkova: Department of Medicine, New York University Langone Health, New York, New York, USA.
Homam Ibrahim: Department of Medicine, New York University Langone Health, New York, New York, USA.
Eugene Yuriditsky: Department of Medicine, New York University Langone Health, New York, New York, USA. ORCID
Yin Aphinyanaphongs: Department of Population Health, New York University Langone Health, New York, New York, USA.
Mark Lifshitz: Department of Pathology, New York University Langone Health, New York, New York, USA.
Feng Xia Liang: DART Microscopy Laboratory, New York University Langone Health, New York, New York, USA.
Julie Alejo: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Grace Smith: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Stefania Pittaluga: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Amy V Rapkiewicz: Department of Pathology, NYU Winthrop Hospital, New York University Langone Health, Mineola, New York, USA.
Jun Wang: Department of Pathology, New York University Langone Health, New York, New York, USA.
Camelia Iancu-Rubin: Department of Pathology, Molecular and Cell-Based Medicine, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ian Mohr: Department of Microbiology, New York University Langone Health, New York, New York, USA.
Kelly Ruggles: Department of Medicine, New York University Langone Health, New York, New York, USA.
Kenneth A Stapleford: Department of Microbiology, New York University Langone Health, New York, New York, USA.
Judith Hochman: Department of Medicine, New York University Langone Health, New York, New York, USA.
Jeffrey S Berger: Department of Medicine, New York University Langone Health, New York, New York, USA. ORCID
OBJECTIVE: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization. APPROACH AND RESULTS: In a cohort of 3915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung tissue, and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43). CONCLUSIONS: Platelet count, size, and maturity associate with increased critical illness and all-cause mortality among hospitalized COVID-19 patients. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.
