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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-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- A nd 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
JournalCritical Care
Volume24
Issue number1
Early online date22 Jul 2020
DOIs
Publication statusE-pub ahead of print - 22 Jul 2020

Bibliographical note

Funding Information: No funding was obtained for this work

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher Copyright: © 2020 The Author(s).

Citation: van Haren, F.M.P., Page, C., Laffey, J.G. et al. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care 24, 454 (2020).

DOI: https://doi.org/10.1186/s13054-020-03148-2

Keywords

  • ARDS
  • COVID-19
  • Nebulised heparin
  • SARS
  • SARS-CoV-2
  • Unfractionated heparin

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