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BLOOD SCIENCES


Five years on from the pandemic there has been relatively little published work regarding a universally accepted clinical biomarker for the identification, detection or monitoring of long COVID patients


compelling evidence indicating that long COVID is a result of post-viral inflammation, while also revealing its intricate complexities. In this study, the Nature Immunology researchers found some unidentified proteins in the long COVID patients could be linked to their specific symptoms. Finding the individual protein should help to divide long COVID patients into different subgroups which could be useful for clinical trials. Also, Professor Eleanor Riley, an Honorary Professor of Immunology and Infectious Disease at the University of Edinburgh, stated that the research data should initiate a sequence of clinical treatment trials for long COVID sufferers with licenced medications that specifically target the immune responses and inflammation. Five years on from the pandemic there has been relatively little published work regarding a universally accepted clinical biomarker for the identification, detection or monitoring of long COVID patients. Research has shown certain individuals


suffering from long COVID exhibited a sustained increase in SARS-CoV-2- specific immunoglobulin G (IgG), despite the absence of detectable virus in their sputum. The analysis of inflammatory markers in nasal fluids revealed no correlation with symptoms. Although the study aimed to understand the inflammatory mechanisms linked to long COVID, it was unable to identify these biomarkers. Therefore, it raises the necessity of using plasma viscosity to detect the continuing and active pattern of inflammatory protein in the blood.


Plasma viscosity testing for COVID-19


The association between COVID-19 and PV has been demonstrated in a 2020 article in The Lancet.21


This research was


carried out on 15 critically ill patients, and all were found to have a PV “exceeding the normal reference range, with results varying from 1.9 - 4.2 mPa.s” reported at 25°C. Most importantly the research indicates a correlation between blood hyperviscosity, and the likelihood of thrombosis as well as the severity of disease in individuals diagnosed with


56 COVID-19.22 This suggests that increased


plasma viscosity could play a role in causing endothelial injury and multiorgan failure in patients with COVID-19. The article published in the Lancet by


Maier et al., (2020) highlighted that the additional research is needed to assess which plasma components, including acute phase proteins like fibrinogen, play a role in the hyperviscosity associated with COVID-19. This research, even in isolation, is certainly convincing evidence that there is an association between COVID-19 and elevated PV. The concentration of plasma fibrinogen is a key determinant of plasma viscosity.23


fibrinogen levels in COVID-19 patients are significant. The article published in The Lancet discusses how ‘mean fibrinogen concentrations in patients with COVID-19 are at the upper limits of normal, presumably as an acute phase response’. Another example is from the research by Han et al., which involved a study of 40 control subjects and 94 patients who tested positive for COVID-19.24


the fibrinogen levels in the COVID-19 positive patients were significantly elevated compared to the healthy control group.


The viscosity of plasma is determined not only by the protein concentration but more importantly by molecular symmetry and molecular weight.


For example, albumin with the


greatest concentration of proteins with a molecular length and diameter ratio


Less likely to get long COVID No pre-existing conditions Male


Affluent


Initial illness asymptomatic Less sick (or asymptomatic)


in the initial COVID-19 illness Fully vaccinated and boosted


Was able to rest during initial illness


Antivirals given promptly during initial illness No reinfection


Table 2. Risk factors for long COVID.11 SEPTEMBER 2025 WWW.PATHOLOGYINPRACTICE.COM


of approximately 2:1 has relatively little effect on viscosity. However, fibrinogen with a much lower concentration has a considerable effect on viscosity. This is due to fibrinogen having a length and diameter ratio of approximately 18:1 and higher molecular weight compared to albumin.25 Therefore, the increased fibrinogen in COVID-19 patients has a significant effect on delivering a high plasma viscosity (PV). The clinical progress and outcome of a COVID-19 infection is extremely variable and was particularly evident prior to the rollout of the vaccines, so the importance of progress predictability is very significant. At Addenbrooke’s hospital, clinical


research was conducted by Gleghorn et al., (2021) to demonstrate the diagnostic potential of PV testing for individuals suspected of having COVID-19.26


A total Therefore, studies into The findings indicated that


of 395 suspected COVID-19 patient samples were examined from April to May 2020. Among these, 224 (56.7%), patients tested negative for COVID-19 using a PCR test. While 171 (43.3%) patients tested positive. All 395 patients also had a plasma viscosity test. A significant difference in plasma viscosity levels was observed when comparing COVID-19 negative patients to those who tested positive. COVID-19 negative individuals exhibited a normal plasma viscosity, averaging 1.62 mPa.s at 25°C, whereas COVID-positive patients had a high plasma viscosity, with an average of 2.00 mPa.s. The analysis of plasma viscosity was conducted utilising the fully automated BV200 Clinical Viscometer.27 Additionally, the study revealed a notably high predictive value for differentiating between high-risk and low-risk patients when utilising PV as the ‘primary marker’. The PV results also suggest that the level at which inpatient admission is required can be directly correlated with the degree of increase in plasma viscosity


More likely to get long COVID Pre-existing conditions Female


Deprived Initial illness multisymptomatic


More sick (perhaps hospitalised) illness during the initial COVID-19


Unvaccinated or under-vaccinated Was unable to rest during initial illness


No antivirals given during initial illness Recurrent COVID-19 infections


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