Analysis of seven trials finds that corticosteroids reduce risk of death by 20 per cent in critically ill COVID-19 patients
Press release issued: 2 September 2020
Corticosteroids reduce the risk of death among critically ill COVID-19 patients by 20 per cent, an analysis of seven trials published today [2 September] in the Journal of the American Medical Association (JAMA) has found. The results of three of the trials included in the meta-analysis are also published in JAMA today.
The study by an international team of scientists, which was co-ordinated by the World Health Organisation (WHO) with analyses led by National Institute for Health Research (NIHR) researchers at the University of Bristol, looked at mortality over a 28-day period after the start of treatment. They found that treatment with one of the three corticosteroids dexamethasone, hydrocortisone or methylprednisolone led to an estimated 20 per cent reduction in the risk of death. This is equivalent to around 68 per cent of patients surviving after treatment with corticosteroids, compared to around 60 per cent surviving in the absence of corticosteroids. The dexamethasone finding is mainly based on results from the RECOVERY trial, which were included in the analysis.
The analysis is the result of unprecedented co-operation between study teams, guideline developers and journals in response to the global pandemic. This ground-breaking collaboration saw results shared between research teams and with guideline developers before they were published, and papers reporting individual trials, the meta-analysis and international treatment guidelines published simultaneously today.
The seven randomised control trials (the best type of study to examine the effect of a medical intervention) recruited 1,703 critically ill patients in total, spanning five continents and including some of the countries hardest hit by COVID-19. The analysis included critically ill patients from the RECOVERY trial, which reported its findings in June 2020.
The mortality results were consistent across the seven trials with two types of corticosteroid, dexamethasone and hydrocortisone, giving similar effects. Too few patients were included in trials of methylprednisolone to allow its effect to be estimated with precision.
There was evidence of benefit from corticosteroids regardless of whether patients were receiving invasive mechanical ventilation at the time they started treatment. The benefit appeared greater among patients who were not so sick that they needed medicine to support their blood pressure, although the results were not definitive in this regard. The effect of corticosteroids appeared similar regardless of age, sex or how long patients had been ill.
Jonathan Sterne, Professor of Medical Statistics and Epidemiology, University of Bristol and Deputy Director of the NIHR Bristol Biomedical Research Centre (NIHR Bristol BRC), said: “Our review is good news in the effort to treat COVID-19, and provides important new information that builds on the findings of the RECOVERY trial. Steroids are a cheap and readily available medication, and our analysis has confirmed that they are effective in reducing deaths amongst the people most severely affected by COVID-19. The results were consistent across the trials and show benefit regardless of age or sex.”
The team behind the review includes the lead researchers for all of the seven trials and scientists from Brazil, Canada, China, France, Spain, the UK and the USA. The work is part of the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) initiative.
John Marshall, Professor of Surgery at the University of Toronto, Senior Scientist at the Li Ka Shing Knowledge Institute at St Michael’s Hospital of Unity Health Toronto, and Co-chair of the WHO Working Group on Clinical Characterization and Management, added: “Even beyond the clear evidence of benefit for an inexpensive and widely available medication, the process of this work – pooling data across seven trials conducted over a period of only three months – highlights the willingness of researchers around the world to share data in a new research model that can bring reliable evidence rapidly to improve the care of patients with COVID-19.”
Janet Diaz, Lead, Clinical response for COVID-19, WHO Emergency Programme, said: “WHO is committed to transforming science to policy in order to save lives. The COVID-19 pandemic has challenged us to work faster, but not to sacrifice quality and standards. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group demonstrates how, in solidarity, science and public health can come together quickly for a common cause. The milestone of pooling of trial data before publication, using that data to inform clinical guidance development and then simultaneous publication of the evidence, evidence synthesis and guidance is unprecedented. I am privileged to have been part of this tremendous collaboration.”
‘Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis’ by Jonathan A C Sterne et al. in JAMA
The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group included: Jonathan A C Sterne, Srinivas Murthy, Janet Diaz, Arthur S Slutsky, Jesús Villar, Derek C Angus, Djillali Annane, Luciano Cesar Pontes Azevedo, Otavio Berwanger, Du Bin, Alexandre B. Cavalcanti, Pierre-Francois Dequin, Jonathan Emberson, David Fisher, Bruno Giraudeau, Anthony C Gordon, Anders Granholm, Cameron Green, Richard Haynes, Nicholas Heming, Julian P T Higgins, Peter Horby, Peter Jüni, Martin J Landray, Amelie Le Gouge, Marie Leclerc, Wei Shen Lim, Flávia R. Machado, Colin McArthur, Ferhat Meziani, Morten Hylander Møller, Anders Perner, Marie W Petersen, Jelena Savovic, Bruno Tomazini, Viviane C. Veiga, Steve Webb and John C Marshall for the WHO COVID-19 Clinical Management and Characterization Working Group.
About the National Institute for Health Research
The National Institute for Health Research (NIHR) is the UK's largest funder of health and care research. The NIHR:
- Funds, supports and delivers high quality research that benefits the NHS, public health and social care
- Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
- Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
- Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
- Partners with other public funders, charities and industry to maximise the value of research to patients and the economy
The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.
This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata
About NIHR Bristol BRC
The National Institute for Health Research Bristol Biomedical Research Centre’s (NIHR Bristol BRC) innovative biomedical research takes science from the laboratory bench or computer and develops it into new drugs, treatments or health advice. Its world-leading scientists work on many aspects of health, from the role played by individual genes and proteins to analysing large collections of data on hundreds of thousands of people. Bristol BRC is unique among the NIHR’s 20 BRCs across England, thanks to its expertise in ground-breaking population health research.
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About the Bristol UNCOVER group
In response to the COVID-19 crisis, researchers at the University of Bristol formed the Bristol COVID Emergency Research (UNCOVER) Group to pool resources, capacities, and research efforts to combat this infection.
Bristol UNCOVER includes clinicians, immunologists, virologists, synthetic biologists, aerosol scientists, epidemiologists and mathematical modellers and has links to behavioural and social scientists, ethicists and lawyers and is supported by a large number of junior academic and administrative colleagues.
Follow Bristol UNCOVER on Twitter at: https://twitter.com/BristolUncover
For more information about the University of Bristol’s coronavirus (COVID-19) research priorities visit: www.bristol.ac.uk/research/impact/coronavirus/research-priorities/