COVID-19 triaging using the inflammatory biomarker suPAR


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

The admission suPAR level is an early indicator of the risk of developing severe respiratory failure, which may require 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
  • Fewer bed-days because more patients can be discharged, leading to reduced healthcare costs

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

“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


How to interpret suPAR results in the COVID-19 department


“It has become clear that suPAR is a very strong prognostic marker, exceeding the prognostic value of all other routinely measured biomarkers in our hospital.”

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

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COVID-19 patient outcome
Need for mechanical ventilation
(exploratory study)

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 al. published in Crit Care 24,187 (2020) evaluated whether the suPAR-level at the time of admission could identify patients who would likely develop SRF within the first coming 2 weeks.

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 cut-off point was later 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%) than 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 AKI.2. It appeared that in patients hospitalised 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 dialysis3.

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/

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