suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19

Izzet Altintas; Jesper Eugen-Olsen; Santeri Seppälä; Jens Tingleff; Marius Ahm Stauning; Nora Olsen El Caidi; Sanaá Elmajdoubi; Hejdi Gamst-Jensen; Mette B Lindstrøm; Line Jee Hartmann Rasmussen; Klaus Tjelle Kristiansen; Christian Rasmussen; Jan O Nehlin; Thomas Kallemose; Harri Hyppölä; Ove Andersen

doi:10.1177/11772719211034685

suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19

Biomark Insights. 2021 Aug 15:16:11772719211034685. doi: 10.1177/11772719211034685. eCollection 2021.

Authors

Izzet Altintas^{1

2}, Jesper Eugen-Olsen¹, Santeri Seppälä³, Jens Tingleff², Marius Ahm Stauning², Nora Olsen El Caidi¹, Sanaá Elmajdoubi¹, Hejdi Gamst-Jensen^{1

2}, Mette B Lindstrøm¹, Line Jee Hartmann Rasmussen^{1

4}, Klaus Tjelle Kristiansen⁵, Christian Rasmussen², Jan O Nehlin¹, Thomas Kallemose¹, Harri Hyppölä³, Ove Andersen^{1

2

6}

Affiliations

¹ Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
² Department of Emergency Medicine, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
³ Emergency Department, Mikkeli Central Hospital, Mikkeli, Finland.
⁴ Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
⁵ Department of Anesthesiology Intensive Care Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
⁶ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Objectives: Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations between plasma suPAR levels (testing the cut-offs ⩽4, 4-6, and ⩾6 ng/mL) with risk of 14-day mortality, and with the risk of mechanical ventilation in patients that tested positive for SARS-CoV-2.

Methods: Observational cohort study of patients presenting with symptoms of COVID-19 at Department of Emergency Medicine, Amager and Hvidovre Hospital, Denmark from March 19th, 2020 to April 3rd, 2020. Plasma suPAR was measured using suPARnostic technologies. Patients were followed for development of mechanical ventilation and mortality for 14 days. Validation of our findings were carried out in a similar sized COVID-19 patient cohort from Mikkeli Central Hospital, Finland.

Results: Among 386 patients with symptoms of COVID-19, the median (interquartile range) age was 64 years (46-77), 57% were women, median suPAR was 4.0 ng/mL (2.7-5.9). In total, 35 patients (9.1%) died during the 14 days follow-up. Patients with suPAR ⩽4 ng/mL (N = 196; 50.8%) had a low risk of mortality (N = 2; 1.0%; negative predictive value of 99.0%, specificity 55.3%, sensitivity 95.2%, positive predictive value 17.4%). Among patients with suPAR ⩾6 ng/mL (N = 92; 23.8%), 16 died (17.4%). About 99 patients (25.6%) tested positive for SARS CoV-2 and of those 12 (12.1%) developed need for mechanical ventilation. None of the SARS-CoV-2 positive patients with suPAR ⩽4 ng/mL (N = 28; 38.8%) needed mechanical ventilation or died. The Mikkeli Central Hospital validation cohort confirmed our findings concerning suPAR cut-offs for risk of development of mechanical ventilation and mortality.

Conclusions: 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 mortality. We suggest cut-offs for identification of risk groups in patients presenting to the ED with symptoms of or confirmed COVID-19.

Keywords: COVID-19; Prognosis; biomarker; mechanical ventilation; suPAR.