One of the biggest challenges facing medical teams treating Covid-19 patients is identifying which ones are likely to suffer the most extreme responses to the virus. Knowing this would make it possible to direct resources more efficiently and begin potentially life-saving treatment earlier.
A large proportion of Covid-19 patients recover without a serious illness, and while certain factors such as age, diabetes or obesity are known to increase the chances that a patient will have more serious complications, these alone do not give a clear prediction of how the disease will progress.
Now scientists believe they have an answer: a simple, affordable well established blood test which essentially measures the thickness of blood and makes it possible to separate the patients that are mildly affected, on the road to recovery or who are likely to deteriorate.
The test in question is clinical viscosity. Scientists have been measuring viscosity for over 100 years and easy to use analyzers have been available for 50 years. Interest in and demand for clinical viscometers has increased following the discovery that severe Covid-19 patients have very significantly raised plasma and serum viscosity levels.
This is reported in the publication of a paper in the Lancet on 25 May 2020 by Cheryl Maier from Emory University, Georgia, Atlanta which demonstrated a dramatic rise of blood viscosity in severe Covid-19 patients. The sickest patients had the highest plasma viscosity levels, more than double normal values, and were also more likely to have a blood clot.
Despite having prescribed medications, known as blood thinners, to prevent blood clots in Covid-19 patients, clotting unusually still occurred. Although referred to as blood thinners, these medications would normally block factors involved in the clotting process as opposed to thinning the blood. As a result of this, it is believed that there is more to investigate within the coagulation process. Hyperviscosity may be an important piece of the puzzle in linking inflammation to clotting.
One thing that stood out was the extremely high levels of fibrinogen, a big sticky protein that increases with inflammation and is a key building block for making blood clots.”
Cheryl Maier, Emory University, Georgia, Atlanta
Performing plasma viscosity measurements is a simple procedure when using viscometers specifically designed for clinical analysis. However, it appears that in north America, (USA and Canada) the majority of clinical laboratories are having to use viscometers that are designed for commercial use or for whole blood analysis. Many publications on clinical viscosity from north America actually report a “relative” viscosity rather than a true viscosity. This is because the analyzers in use have not been designed to be calibrated, to standardized international values, SI units.
The advantage of reporting an absolute viscosity value rather than a relative viscosity, is that absolute viscosities are scientifically a true value, independent of testing method and removes the potential for errors due to contamination of the water standard or the requirement to specify type of water used; e.g. tap water, distilled water, sterile water, de-ionized water etc. Results are then capable of being expressed in an internationally agreed standard format of Pascals second (Pa-s).
The main advantage of using a viscosity system which has been designed, calibrated and controlled for clinical analysis, compared to an adapted industrial viscometer is that a clinical viscometer has increased precision and sensitivity in the clinical relevant range of 1.2 to 10 mPa-s. Commercial viscometers tend to have an operating range of between 10 and 100,000 Pa-s.
Introducing clinical viscometers to pathology laboratories will enable clinicians to rapidly obtain results which can be easily interpreted for both plasma and serum viscosity, which for covid-19 patients will allow a simple rapid decision on which patients require more intensive therapy.
Further advantages include:
- Systems designed for closed vial sampling to reduce biohazard risk to operators
- Systems designed for high sample throughput by fully automated sampling and cleaning
- Automated cleaning designed to remove sample contamination and carry over
- Software designed to highlight clinically abnormal/significant results
- Systems designed to analyse small sample volumes under 0.5 ml
- As only 50µl is used per test, repeat tests can be carried out on 0.5 ml sample
- Integration to clinical laboratory Information Management Systems (LIMS) standard
- Systems designed to be compliant with clinical laboratory regulatory requirements such as ISO:151489
How can a combined plasma and serum viscosity be used and interpreted?
The key to predicting how a patient’s illness is progressing lies in comparing two different viscosity measurements, blood plasma and blood serum both of which can be carried out on modern clinical viscometers.
Plasma viscosity is mainly determined by the level of a blood clotting protein called fibrinogen and antibody concentrations produced by the body's immune system, when it detects and neutralizes harmful substances. Dr.Cheryl Maier’s Covid-19 patients had fibrinogen levels of up to five times the normal value.
Serum is a clear fluid released from blood when blood clots. There is no fibrinogen in serum as this is all used in the production of the clot. Serum viscosity levels are mainly dependent upon the number of antibodies, the ‘fighting proteins’ present. So, an increased serum viscosity can indicate a strong antibody response to Covid-19.
If both plasma and serum results are normal and the patient has a diagnosis of Covid-19, they are probably asymptomatic, an infected patient who does not present with serious symptoms but is possibly a carrier.
If only the serum viscosity is raised, this indicates increased antibody production and may indicate a recovering patient.
If the plasma and serum viscosity analysis reveals that both results are raised, then the patient has raised antibody levels, and may also have a raised fibrinogen level. These patients should have their fibrinogen monitored to see if it is rising or falling.
A raised plasma viscosity with normal serum viscosity indicates raised fibrinogen with no antibody response. These patients are probably deteriorating and will therefore be more likely to require intensive therapy.