September 2, 2020

expert reaction to meta-analysis of trials of corticosteroids and death rate in people hospitalised with severe COVID-19

A meta analysis, published in JAMA, looked at seven trials of corticosteroids for the treatment of severe COVID-19 symptoms, and the associated death rate of hospitalised patients in the UK.

This Roundup accompanied an SMC Briefing

Dr Charlotte Summers, Lecturer in Intensive Care Medicine, University of Cambridge, said:

“This meta-analysis of 7 studies investigating the effect of corticosteroid therapy in critically ill patients with COVID provides further evidence to support the data published previously by the RECOVERY trial investigators, suggesting that steroids are beneficial.  The meta-analysis shows that corticosteroids given to critically ill patients with COVID improves mortality at 28 days.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said: 

“The analysis reported in this paper is a tour-de-force.  The methods are of the very highest standard for combining results from several trials answering the same question.  The trials included in the report are themselves generally also of a high standard – at ‘low risk of bias’. 

“Although a great deal of the data come from the previously reported RECOVERY trial, the findings from the other trials add weight to those earlier results. 

“It must be realised that these results apply to patients who are critically ill – those getting the best care at the time had about a 40% mortality rate within about 4 weeks of their being treated for critical Covid-19 illness. 

“The findings are generally consistent and show that mortality is notably reduced, to about 30-32%.  It is important to acknowledge that, though this is a notable benefit, nearly a third of these critically ill patients were still dying.  While there was no inconsistency between the different corticosteroids used in the trial, the evidence for benefit is strongest for dexamethasone (because it was used in the large RECOVERY trial), methylprednisolone was only used in one small trial and hydrocortisone, though used in three trials, also had less strength of evidence of benefit. 

“So, while there is no evidence that the three different steroids have different effects, it does not mean that they certainly have the same benefit. 

“It is often the case in randomised trials that adverse events are neither recorded nor reported as well as benefits, and this was true here also, but there is no hint of adverse effects being worse for those who received corticosteroids, if anything it is better. 

“Further trials are needed to clarify what is the best dose (there is no sign from these results that higher doses are beneficial) and what is the effect of vasoactive drugs (like adrenaline).  The benefits were less in these patients receiving vasoactive drugs who may be more ill because their blood pressure could not be maintained by use of usual intravenous fluids.  The authors do not comment on whether the vasoactive drugs prevent the corticosteroids working or it is just because of the severity of illness of those patients. 

“It is always good to have confirmatory evidence after encouraging results as were seen with dexamethasone in the RECOVERY trial and this analysis increases confidence that it has a really worthwhile role in critically ill patients with Covid-19.” 

‘Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis’ by The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group was published in JAMA at 15:00 UK time on Wednesday 2 September 2020. 

DOI: 10.1001/jama.2020.17023 

Declared interests 

Dr Charlotte Summers: “I have recruited patients into the REMAP-CAP trial steroid arm (which is included in this meta-analysis).”

Prof Stephen Evans: “No conflicts of interest. I am funded (1 day/week) by LSHTM. They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator or any grants obtained from them. I am the statistician to the “meta-Data Safety and Monitoring Board” for CEPI. I will probably be paid for my attendance at meetings and expenses for travel.” 

None others received.