Digital holo-tomographic 3D maps of COVID-19 microclots in blood to assess disease severity

Abstract

The coronavirus disease 2019 (COVID-19) has impacted health globally. Cumulative evidence points to long-term effects of COVID-19 such as cardiovascular and cognitive disorders diagnosed in patients even after the recovery period. In particular, micrometer-sized blood clots and hyperactivated platelets have been identified as potential indicators of long COVID. Here we resolve individual microclot structures in platelet-rich plasma of donors with different subphenotypes of COVID-19 in a label-free manner, using 3D digital holo-tomographic microscopy (DHTM). Based on 3D refractive index (RI) tomograms, the size, dry mass, and prevalence of microclot composites were quantified and then parametrically differentiated from fibrin-rich microclots and platelet aggregates in the plasma of COVID-19 donors. Importantly, fewer microclots and platelet aggregates were detected in the plasma of healthy controls when compared to COVID-19 donors. Our work highlights the utility of integrating DHTM in clinical settings that may allow the detection of individuals at risk of developing microvascular thrombotic disorders and for monitoring the efficiency of prescribed treatments by screening plasma samples.

Automated microscopic measurement of fibrinaloid microclots and their degradation by nattokinase, the main natto protease

“…As with prions and other amyloid forms of proteins [98,107], that are often highly resistant to proteolysis (e.g. [108,109]), the existence of these 'fibrinaloid' microclots implies their comparative resistance to normal fibrinolysis [110,111], with their precise structures [112] being affected by other small and macromolecules and ions that they may have bound [97,103,[113][114][115][116][117][118][119]. The varieties of stable macrostates into which a given amyloidogenic sequence can fold (even under the same conditions [120,121]) are referred to as different 'strains' [122][123][124][125][126][127][128][129][130][131][132] or 'polymorphisms' [133][134][135][136][137][138][139][140][141][142][143][144], and in some cases are sufficiently stable (i.e.…”