Watch the webinar recording “Catch Covid-19 – Improve your triage”

The suPAR biomarker predicts risk of complications in COVID-19 patients

Peer-reviewed studies have shown that suPAR can identify COVID-19 patients with low-risk as well as high-risk of severe disease progression. Watch the recording to learn how suPARnostic® enables better clinical decisions and how it is used by hospitals in their COVID-19 triaging process directly from doctors in hospitals.

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Key points from the webinar

  • suPAR supports triage decisions across diseases incl COVID-19
  • suPAR level below 4 ng/mL: low risk of adverse outcomes – patients may be discharged and sent home
  • suPAR level above 6 ng/mL: high risk of adverse outcomes – patients should be admitted to care
  • The multicenter study SAVE documents suPAR-guided Anakinra treatment limits development of Severe Respiratory Failure6,7. The international follow-up up study SAVE-MORE accepted by the European Medicines Agency is currently enrolling.

Webinar Q&A session

The suPAR level will change slightly over days depending on the disease progression. E.g., patients in the ICU have suPAR in the double digits, but elevated suPAR levels (most often above 6 ng/ml) are also seen at first presentation in the Emergency Department.

suPAR is more stable in its kinetics that acute markers such as CRP but does increase in patients intubated.

The parameters should be measured when patients attend the Emergency Department for physicians to assess patient’s health. The biomarkers give different knowledge.

PCT or CRP gives good info on possible bacterial infection while suPAR gives better info on prognosis.

Yes, we are looking into Beckman Coulter platforms as well and have done some preliminary work, but a complete validation is not yet carried out.

The prognostic value of suPAR is independent and additive to current score systems such as APACHE, SOFA, and EWS. Thus, by having a suPAR value, you have more knowledge of the disease severity of the patient, See e.g., https://pubmed.ncbi.nlm.nih.gov/30247244/

How to interpret suPAR results in the COVID-19 department


The prognostic biomarker suPAR is currently used across various hospitals in Europe to manage COVID-19 patients.

The admission suPAR level is an early indicator for the risk of developing severe respiratory failure and requiring mechanical ventilation*.

Using admission suPAR levels for COVID-19 patients, physicians may identify low-risk patients for early discharge to reduce the pressure on COVID-19 hospitals, i.e., at emergency departments and in intensive care units 4,5. Furthermore, physicians may identify high-risk patients for early treatment.

COVID-19 hospitals using suPAR for risk stratification may experience:

  • Improved patient care with fewer unnecessary admissions, fewer re-admissions, early treatment intervention, and shorter length-of-stay
  • Empowered clinical staff with more information to make confident decisions reducing stress and uncertainty
  • Reduced healthcare costs

“suPAR can be a strong tool for the much-needed early risk stratification of patients with COVID-19.”

Prof. Ove Andersen, MD, PhD, DmSc, Copenhagen University Hospital Hvidovre, Denmark. suPAR News Vol. 3, June 2020

suPAR is a naturally occurring protein measurable in all humans reflecting immune activation. The protein is associated with inflammation and adverse outcomes across life threatening diseases. suPAR can be measured in clinical routine using the suPARnostic® TurbiLatex product that fits existing hospital work flows and instruments. suPARnostic® TurbiLatex is validated for use on clinical chemistry analysers from Roche Diagnostics, Siemens Healthineers, and Abbott.

COVID-19 patient outcome
Need for mechanical ventilation

n = 57Need for mechanical ventilationNo need for mechanical ventilationPPV/NPV
suPAR > 6 ng/ml183PPV
85.7%
suPAR ≥ 4 and ≤ 6 ng/ml320PPV
13.0%
suPAR < 4 ng/ml013NPV
100.0%
Sensitivity/ Specificity
(suPAR < 4 ng/ml)
Sensitivity
100.0%
Specificity
36.1%

Source: 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 Care24, 187 (2020).


Prediction of severe respiratory failure (SRF) and the need for mechanical ventilation for COVID-19 patients

Cut-off predictor of SRF
suPAR level ≥ 6 ng/ml

Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Rovina N et al. Crit Care. 2020 4(1):187.

A recent study by Rovina et al1 evaluated whether the suPAR-level at the time of admission could identify patients who would likely develop SRF within the first-coming 14 days.

It appeared that a suPAR-level ≥ 6 ng/ml, a cut-off point identified using ROC-analysis, was a strong predictor for developing SRF and requiring ventilation within a relatively short period.

This was confirmed in an international multicenter study showing that very few COVID-19 patients with suPAR below 4.6 ng/ml developed respiratory failure (N=3, 2.6%) compared to patients with suPAR above 6.86 ng/ml (N=53, 44.9%)2.


Prediction of acute kidney injury (AKI) and requirement for dialysis for COVID-19 patients

Patients infected with COVID-19 often develop AKI and many of those patients require dialysis.

In a recent paper, Azam et al investigated the link between a patient’s suPAR level and incidence of in-hospital AKI2. It appeared that in patients hospitalized with COVID-19, the suPAR-level at the time of admission was a strong predictor of developing in-hospital AKI and the need for dialysis. The higher the suPAR-level, the more severe the outcome.

For patients admitted with a suPAR-level < 4.60 ng/ml, only a 6.0% incidence of AKI was found with no patients developing a need for dialysis2. For patients admitted with a suPAR level > 6.86 ng/ml, there was a 45.8% incidence of AKI with 16.1% of those patients requiring dialysis2.

Cut-off AKI incidence increases with suPAR tertiles

  • First tertile: suPAR < 4.60 ng/ml results in 6.0% incidence of AKI and no dialysis requirement

  • Third tertile: suPAR level > 6.86 ng/ml results in 45.8% incidence of AKI and 16,1% requiring dialysis

Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI. Azam TU et al. J Am Soc Nephrol. 2020


* suPAR values should be used in conjunction with clinical findings and the results of other laboratory parameters. suPAR values alone are not indicative of the need for mechanical ventilation.

1. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Rovina N et al. Crit Care. 2020 4(1):187. (LINK: https://pubmed.ncbi.nlm.nih.gov/32354367/
2. Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI. Azam TU et al. J Am Soc Nephrol. 2020 (LINK: https://pubmed.ncbi.nlm.nih.gov/32963090/
3. Soluble Urokinase-Guided Anakinra To Prevent Respiratory Failure In COVID-19: A Single-Arm Trial. Kyriazopoulou E et al. (preprint, link to be provided when available)
4. Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients. Chalkias A et al. Mol Diagn Ther. 2020 (5):517-521. (LINK: https://pubmed.ncbi.nlm.nih.gov/32613288/
5. COVID-19 and pneumonia: a role for the uPA/uPAR system. D’Alonzo D et al. Drug Discov Today. 2020 (8):1528-1534. Review. (LINK: https://pubmed.ncbi.nlm.nih.gov/32562843/
6. Anakinra To Prevent Respiratory Failure In COVID-19. Kyriazopoulou et al. https://medrxiv.org/cgi/content/short/2020.10.28.20217455v1.
7. Anakinra is an interleukin antagonist which is an FDA approved biopharmaceutical drug used to treat rheumatoid arthritis.

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