Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19, 2021, Nishikawa et al

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Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19
Nishikawa, M., Kanno, H., Zhou, Y. et al.

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 micro-angiopathy 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 micro-thrombus 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.

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The article is in glorious technicolour. A few quotes:

Unfortunately, the underlying process of the incidence of COVID-19-associated microvascular thrombosis remains elusive. This is due to the lack of tools to statistically examine the detailed characteristics of platelet activity, or more specifically platelet aggregation (i.e., the initiation of thrombus formation) in vivo

Flow cytometry, on the other hand, enables statistical analysis of large populations of cells by measuring their physical and chemical properties via impedance, scattering, or fluorescence measurements in flow and has been used to identify leukocyte hyperactivity in COVID-19 via fluorescent probes.

However, D-dimer testing does not probe platelet activity in vivo and is not sensitive to microvascular thrombosis including TMA (unless it becomes severe).

Finally, postmortem examination can directly identify microthrombi but is only applicable to dead patients. To date, statistical morphometric understanding of platelet aggregation has been inaccessible and hence overlooked, as optical microscopy (a high-content but low-throughput tool) has been the main method used to examine platelet aggregation in detail thus far

we obtained the landscape of circulating platelet aggregates via massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients.

Our findings (Figs. 3a and 5a) verified earlier reports on the correlation between the VWF level and the severity of COVID-1951 by directly observing the increased concentration of platelet aggregates with its positive link to the severity of COVID-19. Additionally, our findings (Fig. 3a through Fig. 3c) also support a recently suggested mechanism in which platelets are hyperactive during COVID-19, not just via vasculitis, but also via the direct interaction of SARS-CoV-2 with platelets

Our findings suggest that measuring the concentration and distribution of circulating platelet aggregates is a potentially effective approach to evaluating the potential risk of micro-thrombus formation, a condition that can only be verified by postmortem examination.