The landscape of circulating platelet aggregates in COVID-19
Creators
- Zhou, Yuqi1
- Nishikawa, Masako2
- Kanno, Hiroshi1
- Xiao, Ting-Hui1
- Suzuki, Takuma3
- Ibayashi, Yuma1
- Harmon, Jeffrey1
- Takizawa, Shigekazu1
- Hiramatsu, Kotaro4
- Nitta, Nao5
- Kameyama, Risako1
- Peterson, Walker1
- Takiguchi, Jun2
- Shifat-E-Rabbi, Mohammad6
- Zhuang, Yan7
- Yin, Xuwang7
- Rubaiyat, Abu Hasnat Mohammad7
- Deng, Yunjie1
- Zhang, Hongqian1
- Iwasaki, Wataru8
- Yatomi, Yutaka2
- Goda, Keisuke9
- 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
Notes
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