3D Holo-tomographic Mapping of COVID-19 Microclots in Blood to Assess Disease Severity

Area of Science:

• Biomedical Imaging
• Hematology
• Infectious Diseases

Background:

• Long-term health effects of COVID-19, including cardiovascular and cognitive issues, persist post-recovery.
• Micrometer-sized blood clots and hyperactivated platelets are potential biomarkers for long COVID.
• Accurate detection methods are crucial for understanding and managing long COVID.

Purpose of the Study:

• To visualize and quantify microclot structures in COVID-19 patient plasma using label-free 3D digital holo-tomographic microscopy (DHTM).
• To differentiate microclots and platelet aggregates from healthy controls.
• To establish a rapid, clinically applicable imaging workflow for microclot analysis.

Main Methods:

• Utilized 3D digital holo-tomographic microscopy (DHTM) for label-free imaging of plasma samples.
• Quantified microclot size, dry mass, and prevalence using 3D refractive index (RI) tomograms.
• Developed an analysis workflow for parametric differentiation of microclot composites, fibrin-rich microclots, and platelet aggregates.

Main Results:

• Successfully resolved and quantified microclot structures in COVID-19 patient plasma.
• Demonstrated significant differences in microclot and platelet aggregate prevalence between COVID-19 patients and healthy controls.
• Established a workflow with a 2-hour turnaround time from sample preparation to results, suitable for clinical settings.

Conclusions:

• DHTM is an effective label-free technique for characterizing microclots associated with COVID-19.
• Microclots and platelet aggregates are more prevalent in COVID-19 patients, suggesting their role in long COVID.
• The developed rapid imaging and analysis workflow has potential for clinical application in diagnosing and monitoring long COVID.