The landscape of circulating platelet aggregates in COVID-19

Zhou, Y.; Nishikawa, M.; Kanno, H.; Xiao, T.; Suzuki, T.; Ibayashi, Y.; Harmon, J.; Takizawa, S.; Hiramatsu, K.; Nitta, N.; Kameyama, R.; Peterson, W.; Takiguchi, J.; Shifat-E-Rabbi, M.; Zhuang, Y.; Yin, X.; Rubaiyat, A.; Deng, Y.; Zhang, H.; Rhode, G.; Iwasaki, W.; Yatomi, Y.; Goda, K.

A characteristic clinical feature of COVID-19 is the frequent occurrence of thrombotic events. Furthermore, many cases of multiorgan failure are 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 report the landscape of circulating platelet aggregates in COVID-19 obtained by large-scale single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). 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 (less than 1 ug/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 and comparison with other diseases reveal that COVID-19 behaves as a product of thrombosis (localized) and infectious diseases (systemic), as a cause of systemic thrombosis.