Nebulised heparin as a treatment for COVID-19 : Scientific rationale and a call for randomised evidence
Van Haren, Frank M. P. (Intensive Care Unit. Canberra Hospital)
Page, Clive (Sackler Institute of Pulmonary Pharmacology. King's College London)
Laffey, John (Galway University Hospital)
Artigas Raventós, Antoni (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Camprubí-Rimblas, Marta (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Nunes, Quentin (Institute of Systems. Molecular and Integrative Biology. University of Liverpool)
Smith, Roger (St Vincent's Hospital (Sydney))
Shute, Janis (School of Pharmacy and Biomedical Science. University of Portsmouth)
Carroll, Mary (National Infection Service. Public Health England)
Tree, Julia (National Infection Service. Public Health England)
Carroll, Miles (National Infection Service. Public Health England)
Singh, Dave (Medicines Evaluation Unit. University of Manchester)
Wilkinson, Tom (Department of Respiratory Medicine. University of Southampton)
Dixon, Barry (St Vincent's Hospital (Sydney))
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2020
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	COVID-19 ; ARDS ; SARS ; Nebulised heparin ; Unfractionated heparin ; SARS-CoV-2
Published in:	Critical Care, Vol. 24 Núm. 1 (22 2020) , p. 454, ISSN 1466-609X

DOI: 10.1186/s13054-020-03148-2
PMID: 32698853

11 p, 2.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles