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Heparin binding protein in severe COVID-19—A prospective observational cohort study

Lisa Mellhammar, Louise Thelaus, Sixten Elén, Jane Fisher, Adam Linder

2021PLoS ONE28 citationsDOIOpen Access PDF

Abstract

BACKGROUND AND AIMS: Neutrophil-derived heparin binding protein (HBP; also known as azurocidin or CAP-37) is a key player in bacterial sepsis and a promising biomarker in severe infections. The aims of this study were to assess whether HBP is involved in the pathophysiology of COVID-19 and, if so, whether it can be used to predict severe disease preferably using a point-of-care test. METHODS: This was a prospective convenience sample study of biomarkers in patients admitted to Skåne University hospital in Sweden with a confirmed COVID-19 diagnosis. Plasma samples and clinical data were collected within 72h after admission, during hospital stay and at discharge. Plasma HBP concentrations samples were measured both with enzyme-linked immunosorbent assay (ELISA) and with a novel dry immunofluorescence analyzer (Joinstar) point-of-care test. RESULTS: Thirty-five COVID-19 patients were enrolled in the study. Twenty-nine patients had blood samples taken within 72h after admission. We compared the highest HBP value taken within 72h after admission in patients who eventually developed organ dysfunction (n = 23) compared to those who did not (n = 6), and found that HBP was significantly elevated in those who developed organ dysfunction (25.0 ng/mL (interquartile range (IQR) 16.6-48.5) vs 10.6 ng/mL (IQR 4.8-21.7 ng/mL), p = 0.03). Point-of-care test measurements correlated well with ELISA measurements (R = 0.83). HBP measured by the POC device predicted development of COVID-induced organ dysfunction with an AUC of 0.88 (95% confidence interval (CI) 0.70-1.0). CONCLUSIONS: HBP is elevated prior to onset of organ dysfunction in patients with severe COVID-19 using a newly developed point-of-care test and hence HBP could be used in a clinical setting as a prognostic marker in COVID-19.

Topics & Concepts

Observational studyCoronavirus disease 2019 (COVID-19)MedicineHeparin2019-20 coronavirus outbreakCohort studyProspective cohort studySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Internal medicineVirologyOutbreakDiseaseInfectious disease (medical specialty)COVID-19 Clinical Research StudiesSepsis Diagnosis and TreatmentHeparin-Induced Thrombocytopenia and Thrombosis