Understanding microvascular thrombosis in COVID-19 via massive single-cell imaging of circulating platelets

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 present a method for massive image-based profiling, temporal monitoring, and big data analysis of circulating platelets and platelet aggregates in the blood of COVID-19 patients at single-cell resolution, to provide previously unattainable insights into the disease. In fact, our analysis of the image data from 110 hospitalized patients 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, and respiratory condition of patients with COVID-19. Finally, high-dimensional analysis based on deep learning shows that the disease behaves as systemic thrombosis.