Low levels of the prognostic biomarker suPAR are predictive of mild outcome in patients with symptoms of COVID-19 - a prospective cohort study

OBJECTIVE To examine if baseline soluble urokinase plasminogen activator receptor (suPAR) can predict whether patients with COVID-19 symptoms will need mechanical ventilation during a 14-day follow-up. Furthermore, to examine differences in demographics, clinical signs, and biomarkers in patients tested either positive or negative for SARS-CoV-2. DESIGN Prospective cohort study including patients presenting with symptoms of COVID-19. SETTING Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. PARTICIPANTS 407 patients presenting with symptoms of COVID-19 were included from the Emergency Department (ED). Patients were included from March 19 to April 3 and follow-up data was collected until April 17, 2020. MAIN OUTCOME MEASURES Primary outcomes were respiratory failure in patients presenting with symptoms of COVID-19 and in those with a positive SARS-CoV-2 RT-PCR test, respectively. Furthermore, we analysed differences between patients testing positive and negative for SARS-CoV-2, and disease severity outcomes in SARS-CoV-2 positive patients according to baseline suPAR. BACKGROUND Patients admitted to ED with clinical signs or symptoms of COVID-19 infection need a safe and quick triage, in order to determine if an in-hospital stay is necessary or if the patient can safely be isolated in their own home with relevant precautions. suPAR is a biomarker previously shown to be associated with adverse outcomes in acute medical patients. We aimed to examine if suPAR at baseline presentation is predictive of respiratory failure in patients presenting with symptoms of COVID-19. Furthermore, we examined demographic, clinical, and biochemical differences between SARS-CoV-2-positive and negative patients. RESULTS Among the 407 symptomatic patients, the median (interquartile range) age was 64 years (47-77), 58% were women, and median suPAR was 4.2 ng/ml (2.7-6.4). suPAR level below 4.75 ng/ml at admission ruled out respiratory failure during follow-up with an area under the curve (95% CI) of 0.89 (0.85-0.94) and a negative predictive value of 99.5%. Of the 407 symptomatic patients, 117 (28.8%) had a positive RT-PCR test for SARS-CoV-2 and presented with significant differences in vital signs, cell counts, and biomarkers compared to SARS-CoV-2 negative patients. In SARS-CoV-2 positive patients eligible for mechanical ventilation (N=87), 26 (30%) developed respiratory failure. Best baseline predictors of respiratory failure were suPAR with an area under the curve (95% CI) of 0.88 (0.80-0.95), EWS 0.84 (0.75-0.93), lactate dehydrogenase 0.82 (0.71-0.93), and C-reactive protein 0.80 (0.70-0.89). CONCLUSION SARS-CoV-2 affects several patient parameters underpinning the severe impact of the infection. A low suPAR level (<4.75 ng/ml) at baseline is a useful biomarker for aiding clinical decisions including discharge of patients presenting with symptoms of COVID-19.