Blood-based biomarkers for COVID-19

Establishing biomarkers for COVID-19 that indicate which patients are likely to develop severe disease could help clinicians to categorize patients earlier, improve prognosis and prioritize treatment.

Blood-based biomarkers offer a measure of an individual's biochemistry, from a simple patient blood sample, that can help quantify health and disease. The majority of biomarker research and diagnostics have used ELISAs for rapid and quantifiable bioassays from small volumes of patient samples, with the ability to easily adapt this technology to automation and high throughput screening. 

While COVID-19 is typically associated with a respiratory tract infection, some patients progress to acute respiratory distress syndrome, lung injury, shock and multiple organ failure, resulting in substantial death. In addition to the involvement of the respiratory system, increasing research indicates that coagulation abnormalities and inflammatory response are features of severe cases of COVID-19 and that many of the blood-based factors identified may represent viable biomarkers for this disease. 

Coagulopathy biomarkers

COVID-19 has been linked to hypercoagulation.^1-4 Both retrospective and prospective studies have highlighted elevated levels of coagulatory proteins in patients with severe COVID-19 compared to non-severe cases. The most commonly identified coagulopathy biomarkers are elevated D-dimer levels, thrombocytopenia and a mildly prolonged prothrombin time.¹

In one study of patients in Wuhan, China, patients with D-dimer levels over 1 µg/mL (standard range <250 ng/mL) showed an 18-fold increased risk of death.² Thrombocytopenia has been negatively correlated with COVID-19 severity in some studies.² However, other analyses have suggested that true thrombocytopenia, low platelet count, is only present within 5% of patients, while mild thrombocytopenia was observed in 70-95% of severe COVID-19 cases.¹

Together these factors of thrombocytopenia, elevated D-dimer and increased prothrombin time suggest the presence of disseminated intravascular coagulation (DIC). Still, the biomarker levels observed in COVID-19 are not reflective of those seen in other conditions, such as sepsis that also cause DIC. In comparison to sepsis-induced DIC, COVID-19-induced DIC shows much higher levels of D-dimer and reduced levels of thrombocytopenia.¹

It has been suggested that a recent increase in Kawasaki disease-like symptoms may result from coronavirus infection in children.^5-6 Kawasaki disease symptoms include multisystem inflammation,^7,8 and ongoing studies have shown initial results indicate the levels of the coagulatory biomarkers D-dimer, troponin and BNP may be elevated in COVID-19 related Kawasaki disease. Further research will determine whether these markers can be used to indicate patients that are at risk of severe side-effects upon hospital admission.^7-9

Other markers of coagulopathy in COVID-19 include elevated lactate dehydrogenase and ferritin levels. These have been observed across several patient cohorts and indicate thrombotic microangiopathy, which has been seen in some severe cases of COVID-19 post-mortem.¹

Inflammatory biomarkers

Hyperactivation of the inflammatory cascade, leading to cytokine storm, has been extensively cited as a critical biological response in patients with severe COVID-19. Significantly elevated levels of the inflammatory cytokines TNF-α, IL-1, IL-6 have been documented in severe COVID-19 compared to non-severe disease cases.^{1, 10-12}

Many reports show an increase in C-reactive protein (CRP) levels associated with more severe forms of COVID-19,^3,4 with a large proportion of COVID-19 hospital admissions presenting with increased CRP levels.⁴ Elevated CRP was also identified by researchers investigating COVID-19 related Kawasaki disease, with patients exhibiting both elevated CRP and ferritin levels.⁷

Blood-type biomarkers

ABO blood types have previously been linked to various conditions, such as blood group O being protective for cardiovascular disease and thrombosis risk. In COVID-19 analysis of ABO blood types has shown a further protective role for blood type O.^{13, 14} ABO antigens are expressed on epithelial cells, platelets and the blood glycoproteins von Willebrand factor (VWF) and Factor VIII, in addition to red blood cells. Severe COVID-19 pneumonia has been associated with higher levels of both VWF and Factor VIII, and individuals with blood type O have previously been shown to exhibit 20-30% lower levels of VWF compared to non-O type individuals.¹³

SimpleStep ELISA^® for blood biomarkers

Rapid validation of blood biomarkers for COVID-19 could improve patient care and disease outcomes for severe cases. As many of the biomarkers under investigation are commonly elevated in other conditions, assays that target these factors are often already in existence and could be adapted for COVID-19 research. Whether we need to combine new panels of biomarkers or determine new biomarker levels according to the disease characteristics of COVID-19 remains to be seen. Our range of SimpleStep ELISA® kits target many of these potential biomarkers and deliver results in just 90 minutes with a simple single-wash protocol for minimal hands-on lab time. Built on our own in-house recombinant matched antibody pairs these rapid ELISA offer continuity of results across platforms and in transitioning research to the clinic.

See below for our most popular Simple Step ELISA kits blood coagulation.

Abcam’s products are intended for research use only, not for use in diagnostic, therapeutic or any other purposes.

References

1. Levi, M. et al. (2020) Lancet Haematol. 7(6): e438–e440.
2. Sardu, C. et al. (2020) J Clin Med 9(5), 1417
3. Kermali, M. et al. (2020) Life Sci 117788.
4. Guan, W. et al. (2020) NEJM. 382: 18
5. Verdoni, L. et al. (2020) Lancet [Epub ahead of publication]
6. Loomba, R.S. et al. (2020) Cardiol Young 1-5
7. Sample, I. (2020) The Guardian 17 May [https://www.theguardian.com/science/2020/may/17/possible-breakthrough-in-coronavirus-related-syndrome-in-children]
8. Jakob, A. et al. (2020) Eur J Paediatr. 179(3):377-384
9. Kong, W.X. et al. (2019) World J Paediatr 15(2):168-175
10. Chen, L. et al. (2020) Chinese J Tuberculosis Respir Dis 43(0):E005
11. Wang, W. et al. (2020) medRxiv [https://doi.org/10.1101/2020.02.26.20026989]
12. Ruan, Q. et al. (2020) Intensive Care Med. 46(5):846-848
13. O’Sullivan, J.M. (2020) British J Haematol [https://doi.org/10.1111/bjh.16845]
14. Ellinghaus, D. et al. (2020) medRxiv [doi:https://doi.org/10.1101/2020.05.31.20114991]