Microscopic viscoelasticity of COVID-19 blood plasma & serum

Blood plasma (the liquid component of blood without the red blood cells) of COVID-19 patients has been found to very often have a significantly higher viscosity (stickiness) than that of healthy patients. This has further been found to be linked with mortality. It is currently however challenging and time consuming to measure this viscosity. In this project, led by Dr. Kareem Elsayad, and performed together with Doz. Alexander Zoufaly, Dr. Tamara Seitz, and Prof. Manuela Födinger from the Klinik Favoriten, as well as Prof. Judith Aberle from the Medical University of Vienna, a high-resolution optical spectroscopy technique, capable of measuring viscosity in a fraction of a second, will be developed and implemented. This will be used to explore the effects of various factors including temperature and chemical composition on the viscosity for prognostic applications.

This project investigated the potantial of using a light scattering spectroscopy technique - called Brillouin Light Scattering- which can probe the mechanical properties of a material, for identifying any annomalies in the blood plasma of COVID-19 patients. It has previously been reported that COVID-19 patients have a notably higher blood plasma shear viscosity compared to healthy persons, it is however unclear to what extent this is also the case for the longitudinal viscosity measured using Brillouin Light Scattering. Our studies found that while there was on average an increased plasma longitudinal viscosity for patients with severe COVID-19, most notable was that it exhibited a unique dependence on temperature. The anomalous behaviour occurred above around 38C, and was more pronounced in cases of more severe COVID-19 infection. High resolution Brillouin confocal microscopy maps revealed that this anomalous behaviour was accompanied by the emergence of mechanically distinct features measuring several micrometers in diameter. The temperature dependence could be qualitatively described using a simple model for the longitudinal viscosity that considers an increased presence of small inclusions with increasing temperature. Subtle anomalies in the temperature dependence of the shear viscosity of plasma from patients with severe COVID-19 could be described by an analogous model for the shear viscosity. The precise nature of the inclusions still remains ellusive, with speculations being that they may constitute disordered fibrin clots, previously reported in severe COVID-19 patient blood. Some of our most recent studies suggest that these annomalies can persist in a subset of so-called Long COVID patients, and to this end may potentially provide a useful diagnostic tool (both for the severity of COVID-19 and Long COVID, as well as other similar infections). To this end Brillouin Scattering microscopy has several advantages over other techniques in that it is label-free, fast (less than a minute for a measurement), and requires only a small volume of blood plasma (in principle only a few microlitres). Moving towards diagnostic applicaitions we have developed fiber coupled hand-held probes that can measure samples directly inside a small test tube, mitigating the need for any sample mounting. We have also initiated and published calibration-standards and consensus agreements on the measurement and analysis of Brillouin light scattering spectroscopy data, with leading researchers from around the world, to assure measurements between different laboratories can be reliably repeated, and opening the path for medical translation. Overall the project successfully showed that Brillouin Light Scattering spectroscopy of biofluids, and in particular the longitudinal viscosity, can serve as a proxy for the more commonly measured shear viscosity, but contains additional information that is more sensitive to the presence of small inclusions, and that this may have diagnostic and prognostic potential.