Covid-19, or SARS-COV-2, which emerged in late 2019, continues to spread around the world, infecting more than 4.5m people at time of writing, and leading to more than 300,000 deaths. The disease presents a rapid learning challenge for everyone involved in battling with it. Whilst widely regarded as primarily a respiratory disease, it is increasingly being recognised by doctors and scientists as being a systemic infection, which affects not only the respiratory tract, but also the central nervous system, muscular skeletal, renal, haematologic and hepatic systems.
The haematalogic clinical manifestations of Covid-19 are receiving increasing attention, as the scientific and medical community work hard at trying to solve some of the many questions the outbreak poses. For example, why is it that some patients have severe symptoms whilst others have relatively mild symptoms? What is the pathology of the emerging phenomenon of the Kawasaki-like illness linked to Covid-19, which has coronary artery aneurysms as its main complication? (1) Why do a substantial proportion of severe Covid-19 patients develop venous and arterial thromboembolic conditions, and what can we do to improve early recognition of these? (2) Haematological investigations are going to be critical to solving these and other emerging questions. Many of the supporting answers could lie in plasma viscosity.
Plasma Viscosity Testing
Plasma viscosity testing is a sensitive index of plasma protein changes which result from inflammation or tissue damage. The plasma viscosity test is well-established in many NHS hospitals, including some at the forefront of our fight against Covid-19, such as UCLH and St Thomas in London and Addenbrookes, Cambridge. It is a highly accurate indicator of many conditions including any inflammatory disorder (e.g, infection, rheumatoid arthritis), tuberculosis, polymyalgia rheumatica/temporal arteritis. It is also used as a marker for subsequent adverse events in angina and stroke and peripheral occlusive vascular disease16. Plasma viscosity is used as a screening test but, unlike some other indicators and inflammatory markers, it is not affected by haematocrit variations (e.g, anaemia or polycythaemia), or gender, patient age, exercise, pregnancy and age of sample.
Many clinicians recommend the plasma viscosity test for its sensitivity. Other benefits of the test are that plasma viscosity becomes abnormal early in the disease, has a low incidence of false normal values, can be performed on a sample up to 7 days old, is stable, technically reproducible and standardised, and that relatively small changes are significant for any individual.
Covid-19, as with any infection, will cause an increase in the release of acute phase proteins into the circulation. plasma viscosity could be a particularly useful way of measuring this as it is known to show a significant increase in a range of different types of infection, including viral and bacterial.
Early Identification of Severely-Affected Patients
Benson Viscometers, global leaders in the clinical measurement of plasma viscosity, are currently exploring the possibility with partner laboratories of early identification of Covid-19 patients who subsequently go on to develop severe symptoms. This is important because early intervention could increase the likelihood of early recovery.
A symptomatic or confirmed person with Covid-19 will probably have an increased plasma viscosity above the normal range. The patients result is likely to continue rising if their condition deteriorates, until their immune response successfully has the infection under control. A rising daily plasma viscosity may indicate a Covid-19 patient is developing severe symptoms and requires more intensive therapy, such as oxygen support in the form of CPAP or IPPV (ventilation). Similarly, a fall or plateau of plasma viscosity results could be indicative that a patient is over the worst of the infection and that they therefore require a less intrusive approach.
Identification of Recovered Patients
Whilst the patient is in recovery, the plasma viscosity result is likely to begin to fall. However, paradoxically, most patients are likely still to have a positive antigen test. It is proposed that the start of the reduction in viscosity, when measured on consecutive days, could be used as an indicative marker for patient recovery. Hence the patient and their relatives could be informed potentially earlier than at present that there is an indication of recovery, thus reducing anxiety for clinicians and families. If a daily plasma viscosity monitoring routine is started as early as practical, a record of the diseases progress will be available to aid clinicians in determining the most appropriate treatment. With data analysis and experience, they will then be able to forecast and prepare for a worsening condition if the data shows a patient in a deteriorating situation.
The use of plasma therapy on Covid-19 patients is also an area of significant interest. This experimental therapy involves transfusing the antibody-rich blood serum of recovered Covid-19 patients into people who are fighting the illness. A recent study, co-authored by researchers at several institutions including Michigan State University, has shown that the treatment is safe. Plasma viscosity measurement could be an important next step in establishing its effectiveness.
As one of the parameters that raise the plasma viscosity result is the concentration of antibodies in a persons plasma, patients who have recovered from the virus but maintain a raised viscosity result may have high titre (antibody level) which would suggest they could be suitable donors for plasma pheresis to provide antibody therapy protection to other patients.
The hypotheses about plasma viscosity are based on anecdotal evidence and need to be proven through clinical lab trials. Bernie Benson, founder of Benson Viscometers, says “we are seeking to work with clinical and academic groups, potentially to form partnerships to undertake the required analysis. If anyone is planning to undertake a study or trial, we would welcome discussions to progress this. The plasma viscosity test could be specifically used as part of local Covid-19 screening blood work and also to monitor the intensity and progress of the virus episode in a patient, especially given most hospitalised Covid-19 patients are already having daily haematology and chemistry profiles carried out.”
Safe, Inexpensive and Precise
For obvious safety reasons laboratories are applying the principles of closed vial sampling more rigidly now and as a result, any test on a Covid-19 patient that is under filled or requires the sample top to be removed, is generally refused unless in exceptional circumstances. The plasma viscosity analysis is carried out without removing the sample tube cap so is ideally suited to the current circumstances and will provide rapid and straight forward numerical results. There is one normal range for all ages and both sexes (1.5 to 1.72mPA.s) which is already well established and documented for over 50 years, meaning results interpretation is straight forward and there is no requirement to establish a normal range.
Plasma viscosity is a safe and inexpensive test that is capable of a precise result with a high level of confidence within minutes of getting a blood sample to the hospital laboratory. All the NHS clinical viscometers in use are manufactured and supplied by a British company. They are already operational at this moment, programmed and linked via the NHS LIMS (a Laboratory Information Management System), enabling hospitals to effectively manage samples and automatically communicate results and associated data. Therefore, obtaining results for a multi-centre trial is easy.
The role of plasma viscosity in Covid-19 is an avenue which cannot be ignored. In the battle against Covid-19, we need the shared knowledge and contributions of research, statistical analysis and “lessons learned” from a wide range of disciplines. Haematology is increasingly emerging as a discipline with a crucial role to play. The plasma viscosity test will play a significant part in that, as both an individual test, and as part of a routine blood work up panel. To facilitate this, there now needs to be as many plasma viscosity tests performed as possible to provide large volumes of meaningful data which can be evaluated and statistically analysed to assist with Covid-19 but also with any future pandemics. For any laboratories with a reduced routine workload volume, this is an opportune time to utilise available capacity and existing equipment to support finding the answers to Covid-19.
3. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Apr 10. doi: 10.1016/j.thromres.2020.04.013. [Epub ahead of print.] https://www.thrombosisresearch.com/article/S0049-3848(20)30120-1/pdf
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