suPAR is an early predictor of severe respiratory failure in patients with COVID-19

Fri Jun 26 2020

By: Ditte Bjerre, ViroGates

In recent months, the World has been fighting the coronavirus SARS-CoV-2 (COVID-19). Per May 1st, 2020, over three million have tested positive for COVID-19 and more than 200,000 have died.1 Scientists worldwide have since the beginning of the COVID-19 crisis collected data from patients infected with the virus in order to understand the pathology better and learn how to fight the disease.

On April 30, a paper was published in Critical Care authored by Rovina and co-authors2 describing that at the beginning of the illness, patients may experience low-degree fever or flu-like symptoms, but suddenly severe respiratory failure (SRF) can emerge3. Other studies further showed increased levels of circulating D-dimers3,4 suggesting endothelial activation. The urokinase Plasminogen Activator Receptor (uPAR), bound on the surface of the endothelium, may be cleaved early during the disease. This leads to an increase of suPAR5, making suPAR an early predictor of the risk of SRF

To prove that suPAR is an early predictor of the risk of SRF, the Hellenic Sepsis Study Group6 collected clinical information and serum samples within the first 24 hours of admission from patients with infections and at least two signs of the systemic inflammatory response syndrome. Since March 1, 2020, 57 patients with COVID-19 were enrolled. The aim of the study was to evaluate the prognostic value of suPAR admission levels for the development of SRF within 2 weeks. Patients were followed up daily and the development of SRF was recorded. suPAR was measured by the suPARnostic ELISA kit.

The measured suPAR levels were compared to those collected from 15 patients with COVID-19 from the Emergency Department (ED) of Rush University Medical Center, US.

“Admission levels of suPAR were significantly higher among patients who eventually developed SRF.”

Rovina et al., Ref 2

The study showed that the admission levels of suPAR were significantly higher among patients who eventually developed SRF (intubated and mechanically ventilated). It was also demonstrated that patients with suPAR levels ≥6 ng/mL have the highest risk of developing SRF. Finally, suPAR was shown to have a negative predictive value for SRF of 91.7% and a positive predictive value of 85.7%.

Other studies have proposed suPAR to be a biomarker for the risk of death. An analysis of the TRIAGE III trial in 4,420 patients admitted at the ED in Denmark revealed that suPAR ranged between 2.6 and 4.7 ng/mL in 30-day survivors and between 6.7 and 11.8 ng/mL in 30-day non-survivors7. Early increase of suPAR has also been reported to be a predictor of 28-day outcome in sepsis8. Higher plasma levels of suPAR are predictive of and potentially causally involved in kidney disease9 which can be a feature of severe COVID-19 infection.

These findings suggest that suPAR may be able to identify patients who:

  1. Can be safely discharged with low risk of respiratory failure (low suPAR at admission).
  2. In an early stage needs extra attention and are at high risk of developing RF (elevated suPAR at admission).
  3. May benefit of anti-inflammatory treatment (elevated suPAR at admission).8

1. www.worldometers.info/coronavirus
2. Rovina N et al. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit Care 24, 187 (2020).
3 . Guan W et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382;1708-1720 (2020).
4. Pixley RA et al. Interaction of high-molecular-weight kininogen with endothelial cell binding proteins suPAR, gC1qR and cytokeratin 1 determined by surface plasmon resonance (BiaCore). Thromb Haemost 105;1053–9 (2011).
5. Schultz M et al. Early discharge from the emergency department based on soluble urokinase plasminogen activator receptor (suPAR) levels: a TRIAGE III substudy. Dis Markers 3403549 (2019).
6. www.sepsis.gr
7. Hayek SS et al. Soluble urokinase receptor and acute kidney injury. N Engl J Med 382; 416–26 (2020).
8. Giamarellos-Bourboulis EJ et al. Risk assessment in sepsis: a new prognostication score by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care 16;R149 (2012).
9. Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet 395;10229;1033-1034 (2020).

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