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

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.

Antimicrobial Mechanisms and Clinical Application Prospects of Antimicrobial Peptides

“…In clinical studies, neutrophilderived HBP levels were significantly increased in COVID-19 patients who developed organ failure compared with those in patients who did not. These results suggest that HBP levels can predict the development of organ dysfunction caused by COVID-19 [243].…”

Reference Interval for the Axis-Shield Clinical Chemistry Heparin-Binding Protein Assay

“…HBP is also associated with other critically ill conditions, including acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute bacterial meningitis [ 2 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. In addition, a recent study has reported that HBP concentration increased prior to organ dysfunction in patients with severe coronavirus disease (COVID-19) [ 17 ].…”

“…In previous studies, HBP concentration has been measured using a non-automated ELISA [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. An ELISA is a simple and easy procedure to perform, and shows high sensitivity and specificity; it is, however, labor-intensive, has a high possibility of false positive and false negative, and shows antibody instability [ 18 ].…”

“…An ELISA is a simple and easy procedure to perform, and shows high sensitivity and specificity; it is, however, labor-intensive, has a high possibility of false positive and false negative, and shows antibody instability [ 18 ]. Many ELISA kits developed to measure HBP concentration have been used for research purposes, not for clinical use [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Moreover, to the best of our knowledge, the reference interval (RI) of HBP using an ELISA has not been established.…”

Cardiovascular diseases burden in COVID-19

“…The evidence regarding heparin-binding protein (HBP) increase in COVID-19 is not sufficient until these days, while there are a limited number of studies discussing this phenomenon [ [2] , [3] , [4] ]. In order to fully understand the potential role of HBP in pathophysiology of COVID-19 infection, more clinical studies are needed.…”