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Published April 19, 2021 | Version v2
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The landscape of circulating platelet aggregates in COVID-19

  • 1. Department of Chemistry, The University of Tokyo, Tokyo 113-0033, Japan
  • 2. Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
  • 3. Department of Computational Biology and Medical Sciences, The University of Tokyo, 277-8562, Japan
  • 4. Department of Chemistry, The University of Tokyo, Tokyo 113-0033, Japan; Research Center for Spectrochemistry, The University of Tokyo, Tokyo 113-0033, Japan
  • 5. CYBO, Inc., Tokyo 101-0022, Japan
  • 6. Department of Biomedical Engineering, University of Virginia, Virginia 22908, United States
  • 7. Department of Electrical and Computer Engineering, University of Virginia, Virginia 22908, United States
  • 8. Department of Computational Biology and Medical Sciences, The University of Tokyo, 277-8562, Japan; Department of Biological Sciences, The University of Tokyo, Tokyo 113-0033, Japan; Department of Integrated Biosciences, The University of Tokyo, Tokyo 277-8562, Japan
  • 9. Department of Chemistry, The University of Tokyo, Tokyo 113-0033, Japan; Institute of Technological Sciences, Wuhan University, 430072 Hubei, China; Department of Bioengineering, University of California, Los Angeles, California 90095, United States

Description

A characteristic clinical feature of COVID-19 is the frequent occurrence of thrombotic events. Furthermore, many cases of multiorgan failure have been found to be thrombotic in nature. Since the outbreak of COVID-19, D-dimer testing has been used extensively to evaluate COVID-19-associated thrombosis, but does not provide a complete view of the disease because it probes blood coagulation, but not platelet activity. Due to this limitation, D-dimer testing fails to account for thrombotic events which occur despite low D-dimer levels, such as sudden stroke in young patients and autopsy-identified widespread microthrombi in multiple organs. Here we demonstrate large-scale image-based profiling and temporal monitoring of circulating platelet aggregates in the blood of patients with COVID-19 (n = 110) at single-cell resolution. Surprisingly, our analysis shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients, including those who were not clinically diagnosed with thrombosis and those with low D-dimer levels (≤1 µg/mL). Additionally, results indicate a strong link between the concentration of platelet aggregates and the severity and mortality of COVID-19. Finally, high-dimensional analysis reveals that COVID-19 is a highly unique systemic disease having the properties and synergistic interaction of infectious and thrombotic complications

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