Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

Frank M. P. Van Haren, Clive Page, John G. Laffey, Antonio Artigas, Marta Camprubi-Rimblas, Quentin Nunes, Roger Smith, Janis Shute, Mary Carroll, Julia Tree, Miles Carroll, Dave Singh, Tom Wilkinson, Barry Dixon

Research output: Contribution to journalLiterature reviewpeer-review

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Abstract

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.

The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.

These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
Original languageEnglish
Article number454
Number of pages11
JournalCritical Care
Volume24
Issue number1
Early online date22 Jul 2020
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • COVID-19
  • ARDS
  • SARS
  • nebulised heparin
  • unfractionated heparin
  • SARS-CoV-2

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