Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19

Biomed Pharmacother. 2022 Apr:148:112753. doi: 10.1016/j.biopha.2022.112753. Epub 2022 Feb 25.

Abstract

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation.

Method: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed.

Results: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg.

Conclusion: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.

Keywords: BromAc; COVID-19; Mucolytic therapy; SARS-CoV-2; Tracheal aspirate.

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / pharmacology*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Bromelains / administration & dosage
  • Bromelains / pharmacology*
  • COVID-19 / pathology*
  • Chemokines / drug effects*
  • Cytokine Release Syndrome / pathology
  • Cytokines / drug effects*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Combinations
  • Expectorants / pharmacology
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Male
  • Middle Aged
  • Respiration, Artificial
  • Rheology
  • SARS-CoV-2
  • Sputum / cytology*
  • Trachea / pathology
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Chemokines
  • Cytokines
  • Drug Combinations
  • Expectorants
  • Inflammation Mediators
  • Bromelains
  • Acetylcysteine