suPAR-guided triaging and treatment improves patient outcomes in COVID-19

suPAR, a marker of immune activation, is known for its excellent prognostic value and can predict disease severity, readmission, and mortality in patients admitted to the emergency department.
Recently it has been confirmed that suPAR also has superior prognostic value when used for triaging of COVID-19 patients where the question often faced by clinicians is:

• Should the COVID-19 positive patient be discharged because the immune system is strong and can handle the infection, or should the patient be admitted because the immune system is under severe pressure and with a risk of developing respiratory distress syndrome?

Having access to the prognostic information provided by suPAR will support the clinician in making the right call.

Examples of papers that surfaced in 2021 and supported this thesis include:

• Velissaris et al., found suPAR to be higher at admission in COVID-19 patients with chest infection requiring hospitalization, than non-COVID-19 patients³. The authors also noted that most of the COVID-19 patients who died in their study had elevated suPAR levels at the time of admission³.
• Lippi et al., who condensed the content of five studies of suPAR levels in patients with or without severe COVID-19. The pooled analysis showed that suPAR represents a valuable tool for improving risk stratification accuracy and predicting the risk of developing severe consequences of COVID-19⁴.

Implementing suPAR in clinical routine assists the physicians to make clinical decisions by allowing them to triage COVID-19 patients early. Therefore, this leads to faster discharge and earlier patient treatment.

As hospitals experience increased patient crowding leading to a higher workload for the staff, it is more important than ever to quickly determine who can safely be discharged and who should be treated immediately to avoid a severe outcome.

suPAR is a biomarker found in the blood most often measured in the hospital’s central laboratory on high through-put clinical chemistry analyzers from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics and Beckman Coulter. It can also be measured on a benchtop analyzer at the Point-of-Care. Given that, the results are provided fast, allowing for clinical decisions in real-time.

Early suPAR-guided treatment of COVID-19 patients saves lives

If a COVID-19 patient presents with a high suPAR level this indicates an increased risk that the disease will progress into respiratory failure and a poor outcome. It is of utmost importance that these patients are identified early, allowing for the timely onset of targeted treatment.

In December 2020, the SAVE-MORE study involving 37 hospitals was launched. It was designed as a pivotal, confirmatory, phase 3, double-blind randomized controlled multicenter study, with the overall objective to evaluate the efficacy and safety of using the IL-1α/β inhibitor anakinra in COVID-19 patients at risk of progressing to respiratory failure, as identified by plasma suPAR ≥6 ng/mL.

In September 2021, the results of the SAVE-MORE study were published in Nature Medicine⁵. A preprint account of the study was published in May 2021.

Findings

• 64% improved overall clinical outcome for COVID-19 patients⁵
• Significant prevention of death (6.9% vs. 3.2%)⁵
• Significant prevention of progression to severe respiratory failure (31.7% vs. 20.7%)⁵
• Significant increase in the number of patients who were discharged with no evidence of COVID-19 infection by day 28 (26.5% vs. 50.4%)⁵
• Significant reduction in median time of ICU and ED stay (14 vs. 10 days, 12 vs. 11 days, respectively)⁵

suPAR cut-offs for risk stratification in patients with symtoms of COVID-19

The overall objective of the paper by Altintas et al. published in August 2021⁶ was to examine the link between suPAR level cut-offs at ≤4, 4-6, and ≥6 ng/mL and the risk of 14-day mortality, as well as the link between these cut-offs and the need for mechanical ventilation in COVID-19 positive patients.

The study was based on an observational cohort of patients presenting with COVID-19 symptoms at the emergency department at Hvidovre University Hospital between March 19 and April 3, 2020. Validation of the findings was carried out in a similar cohort of COVID-19 patients from the Mikkeli Central Hospital in Finland.

Altintas et al. concluded that patients with symptoms of COVID-19 and suPAR ≤4 or ≥6 ng/mL had low or high risk, respectively, concerning the need for mechanical ventilation or mortality⁶.

Risk for respiratory failure and the need for mechanical ventilation or mortality during the first 14 days

Findings

• Patients with suPAR ≤4 ng/mL had a low risk of mortality (negative predictive value: 99.0%).
• 17.4% of the patients with suPAR ≥6 ng/mL had the need for mechanical ventilation or died.
• None of the COVID-19 positive patients with suPAR ≤4 ng/mL needed mechanical ventilation or died.