John: Hello, I'm John Hilton, senior editor at Cochrane. Cochrane has produced several reviews to help decision makers respond to the COVID-19 pandemic. In August 2021, we published the first version of a living systematic review on systemic corticosteroids and, in this podcast, the first authors, Mirko Griesel of the University of Leipzig Medical Center and Carina Wagner of the University Hospital in Cologne, Germany, talk about the evidence they’ve found and the potential effects of these drugs.

Mirko: Hi Carina, thanks for being here today. Could you begin by telling us why this review is important and giving some background on systemic corticosteroids and COVID-19?

Carina: Thank you, too! We are quite excited to share our findings and thoughts. Corticosteroids are thought to calm down the overreaction of the immune system to the virus, SARS-CoV-2, that causes COVID-19, and by doing so, make the disease less severe. In mid-2020, preliminary results from the large RECOVERY trial provided evidence of a survival benefit for a corticosteroid called dexamethasone in patients who were in hospital and needed oxygen therapy including mechanical ventilation. Since then, this drug and other corticosteroids have been recommended in various guidelines worldwide.

Mirko: That sounds great, so why is it still important to do a review of effectiveness and why are we using a living systematic review approach to do this?

Carina: Yes, you’re right, the idea does sound great, but we know that other interventions for COVID-19 have failed after initial excitment and the evidence for corticosteroids in similar conditions, such as acute respiratory distress syndrome, has been contradictory. Therefore, to confirm the size and potential scale of any benefits, we need corticosteroids to be tested in randomized trials in different stages of disease, different types of patient and different settings where standard of care and resources might not be the same as in the UK, where most of the RECOVERY trial has been done. This variety of evidence then needs to be brought together in a systematic review and the review needs to be kept up to date, which is why we’re doing this living Cochrane Review.
It’s also important to remember the speed with which things have changed during the pandemic and how the evidence on treatments has evolved. This is unprecedented for any area of health care and systematic reviews need to keep pace. The living review also allows us to explore sub-questions like dosing or patient selection in more depth and to reflect on the reactions to the first version of the review.

Mirko: Thanks, let’s move to the evidence that we were able to include in the August 2021 version of the review. Please can you tell us about that.

Carina: We were able to include 11 randomised trials, reporting on approximately 8100 participants, of which one third received steroids. All the studies looked at patients with moderate or severe disease, which means that they had all been admitted to hospitals but with different stages of need for respiratory and other organ support.
Ten trials compared systemic corticosteroids plus standard care to standard care, with a placebo given to the standard care group in some of these. The eleventh trial compared different types of systemic steroids, namely methylprednisolone and dexamethasone.  

Mirko: So, what do these studies tell us about the effects for people with COVID-19?

Carina: For the addition of systemic corticosteroids to standard care, we included data from nine studies, which contained nearly 8000 of the participants. This provides moderate-certainty evidence that steroids probably have a small effect on all-cause mortality in the 28 days after the drugs are started, but we cannot be sure about the effects on ventilator-free days or need for invasive ventilation.
For the trial that compared methylprednisolone and dexamethasone, the number of participants, 86, is too small for reliable conclusions about the effects on mortality or invasive ventilation.

Mirko: What about safety? What evidence is there about any unwanted events?

Carina: Only two studies, with 678 participants, reported serious adverse events and for adverse events more generally and hospital-acquired infections, five trials with 660 participants provide data. However, there is not enough information to make any clear conclusions about this. 

Mirko: Thanks. In summary, what’s our conclusion and what are our next steps?

Carina: The take home message is that systemic corticosteroids appear to have a marginal effect on short-term mortality up to 28 days, which is the basis for their inclusion in treatment guidelines worldwide. However, they are nothing like a magic bullet with the power to change the course of the pandemic. Looking to the future, we know of nine trials that have completed but not yet published their results, and of another 42 ongoing studies. These studies might help resolve some of the remaining uncertainties and we plan to update the review when the accumulating evidence will allow us to derive more certain conclusions.

Mirko: Finally, Carina, if people would like to read the review, how can they get hold of it?

Carina: It’s available online from www Cochrane Library dot com. Typing 'corticosteroids for COVID-19' in the search box will bring up a link to the review.