Point-of-care prognostication in moderate Covid-19: analytical validation and diagnostic accuracy of a soluble urokinase plasminogen activator receptor (suPAR) rapid test

The soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a biomarker for the risk stratification of patients presenting with acute infections. However, most studies evaluating suPAR have used platform-based assays, the diagnostic accuracy of which may differ from point-of-care tests capable of informing timely patient triage in settings without established laboratory capacity. Using samples and data collected during a prospective cohort study of 425 patients presenting with moderate Covid-19 to two hospitals in India, we evaluated the analytical performance and diagnostic accuracy of a commercially-available rapid diagnostic test (RDT) for suPAR, using an enzyme-linked immunoassay (ELISA) as the reference standard. Although agreement between the two tests was limited (bias = -2.46 ng/mL [95% CI = -2.65 to -2.27 ng/mL]), diagnostic accuracy to predict progression to supplemental oxygen requirement was comparable, whether suPAR was used alone (area under the receiver operating characteristic curve [AUC] of RDT = 0.73 [95% CI = 0.68 to 0.79] vs. AUC of ELISA = 0.70 [95% CI = 0.63 to 0.76]; p = 0.12) or as part of a previously published multivariable clinical prediction model (AUC of RDT-based model = 0.74 [95% CI = 0.66 to 0.83] vs. AUC of ELISA-based model = 0.72 [95% CI = 0.64 to 0.81]; p = 0.78). Lack of agreement between the suPAR RDT and ELISA in our cohort warrants further investigation and highlights the importance of assessing candidate point-of-care tests to ensure management algorithms reflect the assay that will ultimately be used to inform patient care. The availability of a quantitative point-of-care test for suPAR opens the door to suPAR-guided risk stratification of patients with Covid-19 and other acute infections in settings with limited laboratory capacity.