[Preprint] Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics, 2023, Illibauer et al.

[SNT Gatchaman]

Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics
Jennifer Illibauer; Tamara Clodi-Seitz; Alexander Zoufaly; Judith H Aberle; Wolfgang J Weninger; Manuela Foedinger; Kareem Elsayad

Blood Plasma Viscosity (PV) is an established biomarker for numerous diseases. While PV colloquially refers to the shear viscosity, there is a second viscosity component--the bulk viscosity--that describes the irreversible fluid compressibility on short time scales. The bulk viscosity is acutely sensitive to solid-like suspensions, and obtainable via the longitudinal viscosity from acoustic attenuation measurements. Whether it has diagnostic value remains unexplored yet may be pertinent given the association of diverse pathologies with the formation of plasma suspensions, such as fibrin-microstructures in COVID-19 and long-COVID.

Here we show that the longitudinal PV measured using Brillouin Light Scattering (BLS) can serve as a proxy for the shear PV of blood plasma, and exhibits a temperature dependence consistent with increased suspension concentrations in severe COVID-patient plasma. Our results open a new avenue for PV diagnostics based on the longitudinal PV, and show that BLS can provide a means for its clinical implementation.


Link | PDF (Preprint: MedRxiv)

 

[SNT Gatchaman]

(Heavy on fluid dynamics physics, which I won't attempt to summarise.)

Already early on in the COVID pandemic it was reported that acute COVID-19 infection is often associated with an increase in shear PV [plasma viscosity] . This was largely attributed to elevated fibrinogen levels in response to infection.

while COVID-19 infection manifests itself as a respiratory disease, its lethality usually stems from the disruption of coagulation processes.

Despite the clear markers of a coagulopathy, the puzzling thing that remained was that pathological analysis in many cases did not reveal the gross clots expected from blood chemistry (D-dimer) analysis

High levels of circulating SF [soluble fibrin monomer complexes] may then lead to the formation of insoluble fibrin protofibrils and subsequently microclots, which have been observed in COVID, as well as Long-COVID, patients

A means for rapidly assessing changes in the physical properties of blood due to soluble or insoluble protein constituents, would thus be highly desirable for deciding and developing optimal treatment strategies and monitoring their effectiveness.

While plasma from COVID patients revealed an elevated mean shear and longitudinal viscosity compared to that of healthy persons, patient-patient variability would limit its stand-alone diagnostic value on an individual basis. We thus in each case focus on the temperature-scaling behavior between 36-40.5°C.

 

[SNT Gatchaman]

(nL is longitudinal viscosity, nS is shear viscosity)

Interestingly we find that at temperatures above ~38°C nL exhibits a saturation that is more pronounced in severe COVID-patient samples, which is also accompanied by a kink in the temperature scaling of nS. A simple theoretical description of the scaling of nL and nS with respect to suspension concentration, suggests our observations may be described by an increase in suspension concentration above ~38°C in severe COVID-patient samples. This is supported by BLS confocal maps which reveal >micron-sized spatial heterogeneities in COVID-patient plasma absent in healthy patient samples, that increase at elevated temperatures, and are accompanied by an increase in the elastic scattering cross-section.

Though a significant increase of FDPs can conceivably result in viscoelastic changes, these in of themselves would be too small in size to explain the observed spatial heterogeneities, and would not explain the lack of any significant hysteresis in up-down temperature sweeps observed (which also rule out the denaturing of proteins).

Our observations are somewhat surprising given that our samples were collected and stored in anticoagulation tubes (Methods), although reports have hinted at the reduced effectiveness of anticoagulants in COVID-19 patients.

While ultrastructural and biochemical studies on suspensions is still needed, one can speculate whether these might be related to crosslinked microfibrin/fibrin microclots reported to exist in COVID patient samples.

Should this be the case this would suggest that the balance between increased fibrin crosslinking (clot formation) and the increased dissociation rate with increasing temperature is perturbed in COVID patient plasma.

Given the persistence of crosslinked fibrin aggregates and microclots also in Long-COVID patient plasma, a means of quantitatively assessing their abundance can be of prognostic and diagnostic value. Longitudinal rheology, may be well suited for this, owing to its acute sensitivity to suspension properties.