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

PLoS One. 2021 Apr 6;16(4):e0249570. doi: 10.1371/journal.pone.0249570. eCollection 2021.

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.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimicrobial Cationic Peptides / blood*
  • Biomarkers / blood
  • Blood Proteins
  • COVID-19 Testing*
  • COVID-19* / blood
  • COVID-19* / diagnosis
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Point-of-Care Testing*
  • Prospective Studies
  • SARS-CoV-2 / metabolism*
  • Severity of Illness Index

Substances

  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Blood Proteins

Grants and funding

Swedish Government Funds for Clinical Research (AL), Region Skåne (AL, LM), the Crafoord foundation (AL), the foundation of Alfred Österlund (AL).