New Data Show Benefit of Steroid Use in Patients With Severe SARS-CoV-2

While there was debate early on in the pandemic, and good reason for clinical study to rule out potential adverse impacts, there is also a precedent for use of steroids to treat respiratory inflammation.

A trio of studies appearing in JAMA today now support steroid use to reduce mortality in patients with severe SARS-CoV-2 infections

The first article highlights WHO Rapid Evidence Appraisal for COVID-19 Therapies [REACT] Working Group findings that administration of systemic corticosteroids, compared with standard care, was associated with lower 28-day all-cause mortality.

The meta-analysis uses pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19.

Patients were randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients).

Out of these 1703 total patients (median age, 60 years) there were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo.

In the 6 trials that reported serious adverse events, 64 occurred among 354 patients randomized to corticosteroids and 80 events occurred in 342 patients randomized to usual care or placebo.

The second article presented findings shared by The Writing Committee for the REMAP-CAP [Randomized, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia] Investigators.

Investigators sought to explore if intravenous hydrocortisone, administered either as a 7-day fixed-dose course or restricted to when shock is clinically evident, improves 21-day organ support—free days in patients with severe SARS-CoV-2 infection.

However, the bayesian randomized clinical trial of 403 patients was stopped early after results from another trial were released.

Still, the ongoing work had thus far concluded treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone resulted in 93% and 80% probabilities of superiority with respect to organ support-free days.

“Although suggestive of benefit for hydrocortisone in patients with severe COVID-19, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions,” authors cautioned.

The third article concerned the CoDEX trial of dexamethasone. Investigators found that the steroid improved outcomes among patients with acute respiratory distress syndrome (ARDS).

In particular, 20mg and 10mg intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.

CoDEX was a randomized, open-label, clinical trial conducted in 41 intensive care units in Brazil from enrollment in mid-April until July 21, 2020.

The trial, like that in the second article, was stopped early following publication of a related study before reaching the intended full sample size of 350 patients.

The intervention involved 20 mg of dexamethasone intravenously daily for 5 days, then 10 mg of dexamethasone daily for 5 days or until ICU discharge, in addition to standard care (151 participants) compared with standard care alone (148 participants).

Due to the early stoppage, 299 patients were enrolled. All 299 completed follow-up.

According to investigators, those randomized to the dexamethasone group had a mean of 6.6 ventilator-free days during the first 28 days compared to a mean of 4 ventilator-free days in the standard care alone group.

On these grounds, the World Health Organization is now expected by some to announce support for use of the treatments.

In summary:

• REACT: “Administration of systemic corticosteroids, compared with standard care, was associated with lower 28-day all-cause mortality.”
• REMAP-CAP: “Treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support—free days within 21 days (not statistically significant, possibly due to premature end of trial.)”
• CoDEX: “Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.”