Systemic Corticosteroids Linked to Lower COVID-19 Mortality

In critically ill COVID-19 patients, administration of systemic corticosteroids compared with standard care was associated with lower 28-day all-cause mortality, according to a recent JAMA Network Open study.

The study gathered data from seven randomized clinical trials that evaluated the efficacy of corticosteroids in 1,703 COVID-19 patients from February 26, 2020, to June 9, 2020.

A total of 678 patients were randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone, while 1,025 patients received standard care.

The association with mortality was 0.64 for dexamethasone compared with standard care, 0.69 for hydrocortisone compared with standard care, and 0.91 for methylprednisolone compared with standard care.

This corresponds to an absolute mortality risk of 32 percent with corticosteroids compared with mortality risk of 40 percent with standard care.

Among the six trials that reported serious adverse events, 64 occurred among 354 patients randomized to corticosteroids, and 80 events occurred among 342 patients randomized to standard care, researchers said.

“Corticosteroids were associated with lower mortality among critically ill patients who were and were not receiving invasive mechanical ventilation at randomization,” JAMA researchers stated.

At the start of the pandemic, data on the efficacy of corticosteroids was limited. But as of July 24, 55 studies of corticosteroids have been registered on ClinicalTrials.gov, researchers said.

At the beginning of September, the World Health Organization (WHO) partnered with Magic Evidence Ecosystem Foundation (MAGIC) to develop guidance on corticosteroids for COVID-19 treatment.

The guidance was based on data from eight clinical trials, including data from the JAMA study. 

The primary outcome for all trials was all-cause mortality up to 30 days after randomization, which was determined before any outcome data were available from any of the studies, researchers said.

The organizations made two recommendations based on these findings, including a strong recommendation for systemic corticosteroid therapy for seven to ten days in patients with severe COVID-19. 

The second recommendation was to avoid use of corticosteroid therapy in patients with non-severe COVID-19.

Given the evidence of an important reduction in the risk of death, the organizations concluded that all fully informed patients with severe COVID-19 would choose treatment with systemic corticosteroids. 

In contrast, the panel said that patients with non-severe COVID-19 would not choose to receive this treatment because of the little benefit and potential harm. 

Other perspectives, patient values, and preferences could also alter decisions.

“Taking both a public health and a patient perspective, indiscriminate use of any therapy for COVID-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially life-saving therapy,” the organizations said. 

There are many opportunities for future research of corticosteroids in coronavirus patients.

This includes research on how future novel immunomodulators interact with systemic corticosteroids, preparation, dosing, and timing of drug initiation, generalizability of study results to populations that were under-represented in trials, and effect on viral replication, the organizations said.

The clinical practice guideline was triggered by preliminary data from a June clinical trial, RECOVERY, which found that dexamethasone improved survival in hospitalized COVID-19 patients. 

At the time, it was the first drug to be shown to improve survival for infected patients.

Overall, dexamethasone reduced the 28-day mortality rate in one-third of patients (17 percent), with a highly significant trend showing the greatest benefit among those patients requiring ventilation.

Out of individuals who received standard care alone, 28-day mortality rate was highest in those who required ventilation (41 percent). The results were intermediate in patients who required oxygen (25 percent) and lowest among those who did not require any respiratory intervention (13 percent), researchers said.