TY - JOUR
T1 - SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19
T2 - The International Study of Inflammation in COVID-19
AU - Vasbinder, Alexi
AU - Padalia, Kishan
AU - Pizzo, Ian
AU - Machado, Kristen
AU - Catalan, Tonimarie
AU - Presswalla, Feriel
AU - Anderson, Elizabeth
AU - Ismail, Anis
AU - Hutten, Christina
AU - Huang, Yiyuan
AU - Blakely, Pennelope
AU - Azam, Tariq U.
AU - Berlin, Hanna
AU - Feroze, Rafey
AU - Launius, Christopher
AU - Meloche, Chelsea
AU - Michaud, Erinleigh
AU - O'Hayer, Patrick
AU - Pan, Michael
AU - Shadid, Husam R.
AU - Rasmussen, Line Jee Hartmann
AU - Roberts, Donald A.
AU - Zhao, Lili
AU - Banerjee, Mousumi
AU - Murthy, Venkatesh
AU - Loosen, Sven H.
AU - Chalkias, Athanasios
AU - Tacke, Frank
AU - Reiser, Jochen
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Eugen-Olsen, Jesper
AU - Pop-Busui, Rodica
AU - Hayek, Salim S.
N1 - Publisher Copyright:
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
PY - 2024/1
Y1 - 2024/1
N2 - Severe 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.
AB - Severe 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.
KW - C-reactive protein
KW - CRP
KW - SARS-CoV-2
KW - SuPAR
KW - infection
KW - interleukin-6
KW - risk prediction
KW - soluble urokinase plasminogen activator receptor
KW - triage
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U2 - 10.1002/jmv.29389
DO - 10.1002/jmv.29389
M3 - Article
C2 - 38235904
AN - SCOPUS:85182623824
SN - 0146-6615
VL - 96
JO - Journal of Medical Virology
JF - Journal of Medical Virology
IS - 1
M1 - e29389
ER -