PMID- 32698853 OWN - NLM STAT- MEDLINE DCOM- 20200728 LR - 20231111 IS - 1466-609X (Electronic) IS - 1364-8535 (Print) IS - 1364-8535 (Linking) VI - 24 IP - 1 DP - 2020 Jul 22 TI - Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. PG - 454 LID - 10.1186/s13054-020-03148-2 [doi] LID - 454 AB - 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. FAU - van Haren, Frank M P AU - van Haren FMP AUID- ORCID: 0000-0001-8037-4229 AD - Australian National University, Medical School, Canberra, Australia. frank.vanharen@anu.edu.au. AD - Intensive Care Unit, the Canberra Hospital, Canberra, Australia. frank.vanharen@anu.edu.au. FAU - Page, Clive AU - Page C AD - Sackler Institute of Pulmonary Pharmacology, King's College London, London, UK. FAU - Laffey, John G AU - Laffey JG AD - Anaesthesia and Intensive Care Medicine, School of Medicine, and Regenerative Medicine Institute (REMEDI) at CURAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland Galway, Galway, Ireland. AD - Department of Anaesthesia, University Hospital Galway, Saolta Hospital Group, Galway, Ireland. FAU - Artigas, Antonio AU - Artigas A AD - Critical Center, Corporacio Sanitaria Parc Tauli , CIBER Enfermedades Respiratorias, Autonomous University of Barcelona, Sabadell, Spain. FAU - Camprubi-Rimblas, Marta AU - Camprubi-Rimblas M AD - Institut d'Investigacio I Innovacio Parc Tauli (I3PT), CIBER de Enfermedades Respiratorias, Sabadell, Spain. FAU - Nunes, Quentin AU - Nunes Q AD - Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. FAU - Smith, Roger AU - Smith R AD - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, Australia. FAU - Shute, Janis AU - Shute J AD - School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth, UK. FAU - Carroll, Mary AU - Carroll M AD - Department of Respiratory Medicine, University of Southampton, Southampton, UK. FAU - Tree, Julia AU - Tree J AD - National Infection Service, Public Health England, Porton Down, UK. FAU - Carroll, Miles AU - Carroll M AD - National Infection Service, Public Health England, Porton Down, UK. FAU - Singh, Dave AU - Singh D AD - Medicines Evaluation Unit, University of Manchester, Manchester, UK. FAU - Wilkinson, Tom AU - Wilkinson T AD - Department of Respiratory Medicine, University of Southampton, Southampton, UK. FAU - Dixon, Barry AU - Dixon B AD - Department of Critical Care Medicine, St Vincent's Hospital, Melbourne, Australia. LA - eng PT - Journal Article PT - Review DEP - 20200722 PL - England TA - Crit Care JT - Critical care (London, England) JID - 9801902 RN - 9005-49-6 (Heparin) SB - IM MH - COVID-19 MH - Coronavirus Infections/*drug therapy MH - Heparin/*administration & dosage MH - Humans MH - *Nebulizers and Vaporizers MH - Pandemics MH - Pneumonia, Viral/*drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC7374660 OTO - NOTNLM OT - ARDS OT - COVID-19 OT - Nebulised heparin OT - SARS OT - SARS-CoV-2 OT - Unfractionated heparin COIS- FvH, CP, JL, QN, RS, BD, JT and MC have nothing to disclose. TW is Chief Investigator of the ACCORD COVID Research Programme. AA and MCR report grants from Grifols, outside the submitted work. JS is the Scientific Director of Ockham Biotech Ltd., a company that owns patents around the use of inhaled heparin. DS reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, personal fees from GlaxoSmithKline, personal fees from Glenmark, personal fees from Gossamerbio, personal fees from Menarini, personal fees from Mundipharma, personal fees from Novartis, personal fees from Peptinnovate, personal fees from Pfizer, personal fees from Pulmatrix, personal fees from Theravance and personal fees from Verona, outside the submitted work. EDAT- 2020/07/24 06:00 MHDA- 2020/07/29 06:00 PMCR- 2020/07/22 CRDT- 2020/07/24 06:00 PHST- 2020/06/16 00:00 [received] PHST- 2020/07/03 00:00 [accepted] PHST- 2020/07/24 06:00 [entrez] PHST- 2020/07/24 06:00 [pubmed] PHST- 2020/07/29 06:00 [medline] PHST- 2020/07/22 00:00 [pmc-release] AID - 10.1186/s13054-020-03148-2 [pii] AID - 3148 [pii] AID - 10.1186/s13054-020-03148-2 [doi] PST - epublish SO - Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.