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

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.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

“…The length of hospital stay in this cohort of COVID-19 patients was mainly determined by the need for oxygen supplementation with gradual phasing out and not the need for rehabilitation, since rehabilitation primarily was carried out at another department. Our results are consistent with previous studies ( 16 , 47 ), but to our knowledge, suPAR has previously not been shown to independently reflect the cohesive length of hospital stay.…”

“…The length of hospital stay in this cohort of COVID-19 patients was mainly determined by the need for oxygen supplementation with gradual phasing out and not the need for rehabilitation, since rehabilitation primarily was carried out at another department. Our results are consistent with previous studies (16,47), but to our knowledge, suPAR has previously not been shown to independently reflect the cohesive length of hospital stay. Nevertheless, suPAR has previously been shown to correlate with a prolonged stay at hospital due to other serious conditions with excessive inflammation, such as cardiac surgery, pneumonia in children, and burn injuries (48)(49)(50).…”

“…The concentration of suPAR in sera correlated with the degree of COVID-19 severity, which has been shown previously ( 47 ). In SARS-CoV-2 infected individuals with low admission levels of suPAR (<4 ng/ml), the risk of needing mechanical ventilation and the 14-day mortality was almost non-existent, while levels between 4–6 ng/ml and especially >6 ng/ml were associated with a significantly increased risk.…”

“…Based on previous research ( 47 ) and guidelines from the manufacturer of the suPAR ELISA, a suPAR of <4 ng/mL supports patient discharge whereas >6 ng/mL supports hospitalisation. Hence, our patients were stratified into three groups based on suPAR levels: low (<4 ng/m), medium (4–6 ng/mL) and high (>6 ng/mL).…”

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

“… 10 suPAR seems extremely promising as a COVID‐19 prognostic marker and may assist in the early selection of patients who can be discharged and continue self‐isolation at home or must be admitted to the hospital and/or intensive care unit. 10 , 11 , 12 , 13 In order to investigate the prognostic ability of suPAR in COVID‐19, we designed the SPARCOL study to assess whether suPAR measured at hospital admission is associated with illness severity in adult patients hospitalized primarily for COVID‐19.…”