SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID‐19: The International Study of Inflammation in COVID‐19

Abstract

AbstractSevere coronavirus disease 2019 (COVID‐19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID‐19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID‐19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C‐reactive protein, interleukin‐6, procalcitonin, ferritin, and D‐dimer. In‐hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL‐6 (0.614), D‐dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%–98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%–96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%–96.7%) and NPV of 95.5% (93.1%–97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low‐risk patients with COVID‐19.