Abstract
A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.
Highlights
A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis
We acquired 25,000 bright-field images of single platelets and platelet aggregates in the blood of hospitalized patients (n = 110) who were clinically diagnosed with COVID-19 based on their reverse transcriptionpolymerase chain reaction (RT-PCR) test results (Fig. 2a and Supplementary Data 1)
Negative control image data were obtained from healthy subjects under the same sample preparation and image acquisition conditions on the same day to mitigate potential bias in the image data that may have come from experimental variations in blood draw, sample preparation, optical alignment, and hydrodynamic focusing conditions and to maintain the state of platelet aggregation in vivo while minimizing the effect of aggregation in vitro
Summary
A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. Earlier autopsy reports on patients who died with COVID-19 have shown widespread thrombotic microangiopathy (TMA) characterized by extensive diffuse microthrombi present within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure[1,3,7–11]. This is aligned with respiratory failure due to severe diffuse alveolar damage being the primary cause of death in COVID-193,10. Post-COVID-19 syndrome manifested by persistent and prolonged aftereffects has been reported to be linked to COVID-19-associated microvascular thrombosis[15,16] This is due to the lack of tools to statistically examine the detailed characteristics of platelet activity, or platelet aggregation (i.e., the initiation of thrombus formation)[17–20] in vivo. Statistical morphometric understanding of platelet aggregation has been inaccessible and overlooked, as optical microscopy (a high-content but lowthroughput tool) has been the main method used to examine platelet aggregation in detail far[26,32]
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