Coronavirus Disease (COVID-19) Feb 2021

Coronavirus Disease (COVID-19) is causing the worst global pandemic in living memory. It is responsible for putting huge strain on health services around the world and has currently caused the deaths of over 2.3 million people.

COVID-19 spreads primarily through small droplets of virus infected saliva or discharge from the nose when coughing or sneezing. The virus may also spread via contaminated surfaces, although this is not thought to be a significant mode of transmission. Carriers of the disease may be asymptomatic for several days which means they could be spreading the virus without even knowing it.

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.

The Link to Plasma Viscosity

The association between COVID-19 and plasma viscosity (PV) has been demonstrated in a 2020 article in The Lancet. The research was carried out on 15 critically ill patients and all were found to have a PV ‘exceeding 95% of normal……ranging from 1.9 – 4.2 centipoise (cP; normal range 1.4 – 1.8)’ (Maier et al, 2020:1759). It was also found that there was a strong correlation between a raised PV and the severity of the condition.

Dr.Cheryl Maier’s research, even in isolation, demonstrates that there is an association between COVID-19 and PV.

The relevance of PV testing has been recognised for nearly 40 year (Harkness, 1971:171) and subsequent research has shown that it has significant clinical applications, of which the prognosis of COVID-19 patients is the latest.

Initially, COVID-19 was considered to be a serious pulmonary illness. However, the disease demonstrated its ability to be most destructive as a severe haematological condition, calling for a radical change in approach.

Using other methods, such as ESR and CRP, for measuring inflammation alone would be insufficient and would not report these key viscosity levels. Only clinical viscosity testing provides the detailed valuable hyperviscosity information required by clinicians.

It would be easy to dismiss the plasma viscosity test as you would normally expect to see an increase in blood viscosity levels due to the body fighting an infection. However, scientists are realising that by comparing the viscosity of two similar but different blood components, they could have a valuable aid in predicting how a patient’s illness is progressing, enabling timely and effective interventions to be made.

There is also evidence to suggest that shortly before death, PV levels will decrease dramatically. This indicates that the viscosity levels of plasma may be higher in COVID-19 patients during the disease yet with a noticeable lowering if they are likely to die soon. This solidifies the research from Maier et al. that the PV correlates with severity (Maier et al, 2020).

Considering that COVID-19 is a relatively new-found disease, this range of research into its association with PV appears to be of significant value and increased clinical importance may be identified from further research.

Figure: Plasma viscosity and Sequential Organ Failure Assessment (SOFA) score in 15 critically ill patients with COVID-19. All patients had plasma viscosity levels above the normal reference range (1.4-1.8 centipoise, cp). Plasma viscosity was strongly correlated with SOFA scores by Pearson correlation, r = 0.841, R2 = 0.7072, p<0.001. Grey circles indicate patients without known thrombotic complications and black squares indicate patients with known thrombotic complications (Maier et al, 2020:1759)

The Role of Fibrinogen

The publication of a paper in the Lancet on 25 May 2020 by Dr Cheryl Maier from Emory University, Georgia, Atlanta reported 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.

Covid patients are normally prescribed prophylactic anticoagulants, low molecular weight heparin, to prevent thrombosis. Patients with severe symptoms have been reported to develop multiple thromboses even when given this prophylaxis. It appears that the coagulation process in Covid-19 patients is sufficiently enhanced to overcome these low levels of anticoagulation.

Plasma viscosity is mainly determined by the level of a blood clotting protein called fibrinogen and antibody concentrations; proteins produced by the body’s immune system.
The fibrinogen concentration in plasma is the main determinant of plasma viscosity’ (Otto et al, 2000:810). Dr.Cheryl Maier’s Covid-19 patients had fibrinogen levels of up to five times the normal value. As hyperviscosity can be caused by high fibrinogen levels this may be an important piece of the blood clotting puzzle. This would indicate that studies into the clinical viscosity levels of COVID-19 patients are not only necessary, but are needed now.

For example an article from The Lancet Haematology, discusses how ‘mean fibrinogen concentrations in patients with COVID-19 are at the upper limits of normal, presumably as an acute phase response’ (Levi et al, 2020:e438). Another example comes from a study of 40 control subjects and 94 COVID-19 positive patients, where the latter had fibrinogen values that ‘were substantially higher than those in healthy controls’ (Han et al, 2020:1116).

Whilst both fibrinogen and antibody levels affect the plasma viscosity so, a raised plasma viscosity cannot be attributed to fibrinogen concentrations without further testing. Although this is possible, fibrinogen analysis requires further blood samples to be taken and is a relatively expensive test. This is where a simple, cost-effective serum viscosity test comes in.

Serum Viscosity

Serum is the clear fluid released from blood when it clots. There is no fibrinogen in serum as this is all used in the process of coagulation. 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.

IgM is usually the first antibody produced by the immune system when a virus attacks. A positive IgM test indicates that you may have been infected and that your immune system has started responding to the virus. An increase production of an IgM paraprotein can increase serum viscosity.

Comparing and Utilising Both Plasma and Serum Viscosity

Performing both a serum and a plasma viscosity test on samples from the patient and comparing the results is a simple procedure when using Clinical Viscometers.

This would again indicate that studies into the clinical viscosity levels of COVID-19 patients are necessary and are needed now.

At a time when resources are challenged, it would be understandable for laboratories and research centres to feel they did not have the appropriate time and materials to progress these studies. The question should be, can we afford not to?

If you want to explore how you can progress this vital haematological investigation of how clinical viscosity can give vision and insight to COVID-19, then please contact us.

References

• Maier, CL., Truong, AD., Auld, SC., Polly, DM., Tanksley, CL. and A. Duncan (2020) COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?. The Lancet, 395 (10239), pp. 1758-1759.

• Otto, C., Richter, WO. and P. Schwandt. (2000) Contribution of fibrinogen and lipoproteins to plasma viscosity in hypercholesterolemia and hypertriglyceridemia: evaluation by selective depletion of low-density lipoproteins or fibrinogen. Metabolism, 49 (6), pp. 810-813.

• Levi, M., Thachil, J., Iba, T. and JH. Levy (2020) Coagulation abnormalities and thrombosis in patients with COVID-19. The Lancet Haematology, 7 (6), pp. e438-e440.

• Han, H., Yang, L., Liu, R., Liu, F., Wu, KL., Li, J., Liu, XH. and CL. Zhu (2020) Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clinical Chemistry and Laboratory Medicine, 58 (7), pp. 1116-1120.

• Tang, N., Li, D., Wang, X. and Z. Sun (2020) Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis, 18 (4), pp. 884-847.

• Harkness J. The viscosity of human blood plasma: its measurement in health and disease. Biorheology 1971; 8 (3): 171–93.