Systemic corticoids cut death risk in critically ill COVID-19 patients

The systemic use of corticosteroids lowers 28-day all-cause mortality among patients with the novel coronavirus disease (COVID-19), as opposed to usual care or placebo, according to the REACT* meta-analysis presented at the recently concluded eCritical Care Reviews Meeting 2021 (eCCR21).

“The estimated effect of hydrocortisone, although imprecisely estimated, was consistent with that of dexamethasone. There was no suggestion that higher-dose corticosteroids had greater benefit, and no suggestion of an increased risk of serious adverse events,” said lead author Jonathan Sterne from the Department of Population Health Sciences, Bristol Medical School.

Drawing from seven randomized clinical trials, this prospective meta-analysis looked at the efficacy of using corticosteroids in 1,703 critically ill COVID-19 patients. Dexamethasone, hydrocortisone, and methylprednisolone were administered to 678 patients, while the remaining 1,025 received usual care or placebo.

A total of 222 deaths were recorded among patients randomized to receive corticosteroids, as opposed to 425 deaths among placebo/usual care comparators. Fixed-effects meta-analysis showed that the systemic medication significantly lowered the odds of all-cause mortality by nearly 40 percent (odds ratio [OR], 0.66, 95 percent confidence interval [CI], 0.53–0.82; p<0.001). [JAMA 2020;324:1330-1341]

In absolute terms, “for an assumed mortality risk of 40 percent with usual care or placebo, the corresponding mortality risk with corticosteroids is 31 percent,” corresponding to a 9-percent absolute reduction, said Sterne. Six of the seven included studies showed low risk of bias for mortality analysis.

Looking at each type of corticosteroid individually, the researchers found that dexamethasone likewise significantly suppressed the odds of all-cause mortality (three trials; OR, 0.64, 95 percent CI, 0.50–0.82).

Similar magnitudes and directions of effect were found for hydrocortisone (three trials; OR, 0.69, 95 percent CI, 0.43–1.12) and methylprednisolone (one trial; OR, 0.91, 95 percent CI, 0.29–2.87), though estimates were less precise and significance for these subgroup analyses could not be established.

Sterne cautioned that they were unable to secure enough data to draw conclusions regarding the relative efficacies of different doses. “But to the extent that we can say anything, there’s no suggestion of further reductions in mortality associated with high doses compared with low doses.”

Six trials looked at serious adverse event after treatment. Overall, 64 such events occurred among the 354 patients on systemic corticosteroids, as opposed to 80 events in 342 patients given usual care/placebo.

The present meta-analysis was prospective and collaborative. Through online registries, the authors identified trials before results had been published and worked with the individual groups and investigators to optimize the protocol for the meta-analysis. This process ensured that the pooled analysis would be as complete and as unbiased as possible, said Sterne.

“This was a successful collaboration … convened by the [World Health Organization], and involved the trial investigators, methodologists, guideline developers, and medical journals,” he added.

*The WHO Rapid Evidence Appraisal for COVID-19 Therapies