Exploring suPAR as the Leading Indicator for COVID-19 Risk Assessment

Fri Jun 26 2020

By: Jesper Eugen-Olsen, PhD, Copenhagen University Hospital Hvidovre, Denmark

The COVID-19 pandemic has overwhelmed hospitals, creating a critical need for markers that can quickly identify patients at risk of severe disease. Such markers would help in discharging patients unlikely to develop serious symptoms and isolating those who need more intensive care or ICU admission. Predicting disease progression with biomarkers could streamline this process.

Reports indicate that severe COVID-19 cases often involve hyper-immune responses and cytokine storms. However, cytokines’ instability and sensitivity to sample handling render them impractical for routine clinical decisions.

Research has linked several routine biomarkers to severe COVID-19 outcomes, including increased levels of white blood cells, reduced lymphocytes and platelets, and elevated alanine aminotransferase, creatinine kinase, lactate dehydrogenase, ferritin, C-reactive protein, Interleukin-6, and D-dimer. These could be key in managing patient care during the pandemic.

“It is expected that suPAR is a strong biomarker of disease severity and progression in patients with COVID-19.”

Dr. Jesper Eugen-Olsen

We speculate that suPAR, a stable biomarker of immune activation, is a strong biomarker for development of severe disease and respiratory failure in patients with COVID-19 symptoms (Fig. 1). There are at least five reasons why suPAR may be a suitable marker for this purpose:

  1. suPAR is a marker of chronic inflammation. Patients with high suPAR have a chronically activated immune system that is not capable of fighting disease.
  2. suPAR is elevated in elderly with comorbidities and capture the most fragile patients. In acute medical patients in general, suPAR is a strong marker of 30- day readmission and mortality.3,4
  3. suPAR has been investigated in several viral infections, including HIV, HCV, Crimean-Congo hemorrhagic fever, and hantavirus. In all cases, suPAR is associated with clinical severity and mortality.5,6,7,8
  4. suPAR is elevated and associate to disease severity in patients with respiratory diseases including pneumonia9 and COPD10, and predicts risk of acute respiratory distress syndrome in patients with sepsis.11
  5. The SARS-CoV-2 viral infection is likely to induce highly elevated suPAR in the most severe cases. This may cause acute kidney injury12,13, a disease often observed in COVID-19 patients in the intensive care department.
Discharge decision with suPAR

Fig. 1. Hypothesis: the baseline plasma suPAR level can differentiate whether patients with COVID-19 will have a mild or a severe outcome of the infection.

In summary, it is expected that suPAR is a strong biomarker of disease severity and progression in patients with COVID-19 and may provide an important tool for the managing of patients suspected of having this virus.

Clinical studies documenting this are warranted.

1. Pedersen SF et al. SARS-CoV-2: a storm is raging. J Clin Invest 130;5;2202-2205 (2020).
2. Henry BM et al. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a metaanalysis. Clin Chem Lab Med 58;7;1021-1028 (2020).
3. Rasmussen LJH et al. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study. Emerg Med J 33;11;769-775 (2016).
4. Rasmussen LJH et al. Combining national early warning score with soluble urokinase plasminogen activator receptor (suPAR) improves risk prediction in acute medical patients: a registry-based cohort study. Crit Care Med 46;12;1961-1968 (2018).
5. Hoenigl M et al. Soluble urokinase plasminogen activator receptor is predictive of non-AIDS events during antiretroviral therapy-mediated viral suppression. Clin Infect Dis 69;4;676-686 (2019).
6. Oliveira I et al. Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study. BMJ Open 14;2;6 (2012).
7. Yilmaz G et al. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol. 50;3;:209-11 (2011).
8. Outinen TK et al. Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection. PLoS One 8;8; (2013).
9. Çitlenbik H et al. Levels of Soluble Urokinase Plasminogen Activator Receptor in Pediatric Lower Respiratory Tract Infections. Pediatr Allergy Immunol Pulmonol 32;3;121-127 (2019).
10. Håkansson KEJ et al. High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD. Int J Chron Obstruct Pulmon Dis 15;733-743 (2020).
11. Chen D et al. Serum plasminogen activator urokinase receptor predicts elevated risk of acute respiratory distress syndrome in patients with sepsis and is positively associated with disease severity, inflammation and mortality. Exp Ther Med 18;4;2984-2992 (2019).
12. Hayek SS et al. Soluble Urokinase Receptor and Acute Kidney Injury. N Engl J Med 382;5;416-426 (2020).
13. Yang X et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med pii: S2213-2600;20;30079-5 (2020).


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