BackgroundAKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19–related AKI is unknown.MethodsIn a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI.ResultsOf the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups.ConclusionsAdmission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.

Background SARS-CoV-2 strains healthcare capacity. Better risk stratification, with discharge of patients with a predicted mild disease trajectory can ease this burden. Elevated blood soluble urokinase plasminogen activator receptor (suPAR) has previously been shown associated with risk of intubation in confirmed COVID-19 patients. Objective To evaluate if point-of-care measures of suPAR in patients presenting at the emergency department (ED) with symptoms of COVID-19 can identify patients that can be safely discharged. Methods Observational cohort study including all patients in the ED with symptoms of COVID-19 from March 19 th to April 3 rd , 2020. Soluble urokinase plasminogen activator receptor was measured at first presentation. Review of electronic patient records 14 days after admission were used to assess disease trajectory. Primary endpoints were mild, moderate, severe, or very severe trajectory. The predictive value of suPAR, National early warning score (NEWS), C-reactive protein (CRP), and duration of symptoms (DOS) was calculated using receiver operating characteristics (ROC). Results Of 386 patients, 171 (44%) patients had a mild disease trajectory, 79 (20%) a moderate, 63 (16%) a severe, and 73 (19%) a very severe disease trajectory. Low suPAR was a strong marker of mild disease trajectory. Results suggest a cut-off for discharge for suPAR<2.0 ng/ml if suPAR is used as a single parameter, and 3.0 ng/ml when combined with NEWS=<4 and CRP<10 mg/l- Conclusion suPAR is a potential biomarker for triage and safe early discharge of patients with COVID-19 symptoms in the ED. suPAR can be used even before SARS-CoV-2 status is known.

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.

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Background Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID‐19. Whether suPAR levels identify patients with COVID‐19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID‐19 with suPAR and D‐dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine‐Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D‐dimer levels. There was a positive association between suPAR and D‐dimer (β=7.34; P =0.002). Adjusted for clinical covariables, including D‐dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51–4.75]; P <0.001). Findings were consistent when stratified by D‐dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D‐dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D‐dimer in patients hospitalized for COVID‐19. Combining suPAR and D‐dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04818866.

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.