Detection of Long COVID Microclots using Pulsed Speckle Contrast Optical Spectroscopy

Circulating microclots are increasingly linked to long COVID as well as its persistent symptoms such as fatigue, cognitive deficits, and cardiovascular complications. These conditions can become debilitating or even life-threatening, which create an urgent need for rapid and reliable detection and monitoring tools. In this study we investigate pulsed speckle contrast optical spectroscopy (p-SCOS) as a non-invasive and label-free method to detect microclots in biofluids. Microclots at four concentrations (21k, 91k, 400k, and 1.7M microclots/mL), representing levels from healthy individuals to acute coagulopathic states, were generated using a freeze-thaw method. We measured speckle contrast under flowing conditions in a custom-made flow phantom. In phosphate-buffered saline (PBS) and plasma, increasing microclot concentration consistently led to measurable decreases in speckle contrast. The measurement differentiated between low and high clot burdens in transparent media which highlights its potential for microclot monitoring. In comparison, no detectable changes were observed in whole blood, likely due to dominant scattering from red blood cells masking microclot effects. Overall, our findings demonstrate the feasibility of p-SCOS as a rapid and label-free tool for microclot detection and monitoring in transparent biofluids.