The pathophysiology of severe COVID-19 has been implicated to involve neutrophil activation in the blood and in the lungs and endothelial dysfunction.
Heparin binding protein (HBP) is a neutrophil protein that plays an important role in bacterial sepsis and is a promising biomarker in severe infections. Syndecans and glypicans are potential markers of sheeding of the glycocalyx and endothelial dysfunction.
The primary aims of this study were to assess whether HBP or syndecans and glypicans are involved in the pathophysiology of COVID-19 and if so, whether they can be used to predict severe disease preferably using a point-of-care test (POC) that can substitute more time-consuming analysis with enzyme-linked immunosorbent assay (ELISA).
Methods: A prospective convenience sample study of biomarkers. The main cohort consisted of patients admitted to hospital with a confirmed COVID-19 diagnosis. Samples and clinical data were collected at admission, during admission and at discharge and samples were analyzed with ELISA kit (Axis-Shield Diagnostics) for measuring HBP concentration and a novel dry immunofluorescence analyzer (Jet-iStar 800) (Joinstar) for point-of-care testing.
Results: Thirty-five COVID-19 patients were prospectively enrolled in the study. HBP was significantly elevated in COVID-19 patients with organ dysfunction (n= 23) compared to those without organ dysfunction (n=6), 24.7 ng/mL (95% CI 17.3-48.4) vs 10.6 ng/mL (95% CI 6.2-17.1 ng/mL), p=0.03. Syndecan-1 and Glypican-4 were not significantly elevated in patients with organ dysfunction. Syndecan-1, 62.1 ng/mL (44.4-102.0) vs 57.5 ng/mL (95% CI 46.0- 63.7), p=0.44 and glypican-4, 3292.4 pg/mL (95% CI 1707.5- 6790.6) vs 3962.7 pg/mL (95% CI 2653.6- 5823.5), p=0.80. The point-of-care (POC) HBP test showed good correlation to the standard ELISA with an R-value of 0.83. HBP measured by the POC device predicted development of COVID-induced organ dysfunction within 72 hours with an AUC of 0.88.
Conclusions: The neutrophil-derived 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.