May 20, 2020

Early short course of methylprednisolone improves outcomes in moderate to severe COVID-19

By Denise Baez

NEW YORK -- May 20, 2020 -- An early, short course of methylprednisolone in patients with moderate to severe coronavirus disease 2019 (COVID-19) reduced escalation of care and improved clinical outcomes, according to a study published in Clinical Infectious Diseases.

Raef Fadel, DO, Henry Ford Hospital, Detroit, Michigan, and colleagues conducted a single pre-test, single post-test quasi-experiment from March 12, 2020, to March 27, 2020 in 213 adult patients with moderate or severe COVID-19. All patients had radiographic evidence of bilateral pulmonary infiltrates, and required oxygen by nasal cannula, high-flow nasal cannula (HFNC), or mechanical ventilation.

Moderate COVID-19 was treated with hydroxychloroquine 400 mg twice daily for 2 doses on day 1, followed by 200 mg twice daily on days 2 to 5. Beginning on March 20, 2020, patients with moderate COVID-19 who required ≥4 litres of oxygen per minute on admission, or who had escalating oxygen requirements from baseline, were recommended to receive a short-course of intravenous methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Patients who required intensive care unit (ICU) admission were recommended to receive the above regimen of hydroxychloroquine and IV methylprednisolone for 3 to 7 days. ICU patients were also evaluated for tocilizumab on a case-by-case basis. Oral switch was performed to prednisone at a ratio of 1 to 1 when determined clinically appropriate by the primary medical team.

Of the 213 patients, 81 received standard care (supplemental oxygen, HFNC, invasive ventilation, antibiotic agents, antiviral agents, vasopressor support, and renal replacement therapy) and 132 received standard care plus early, short-course of methylprednisolone.

The early corticosteroid group had a greater proportion of corticosteroids initiated within 48 hours of presentation (12.4% vs 41.7%; P< 0.001), with a median time to initiation of 2 days compared with 5 days in the standard care group. The median time to hydroxychloroquine initiation was greater in the standard care group.

The composite endpoint of escalation of care from ward to intensive care unit, new requirement for mechanical ventilation, and mortality occurred at a significantly lower rate in the early corticosteroid group versus the standard care group (34.9% vs 54.3%; P = 0.005). 

This treatment effect was observed within each individual component of the composite endpoint. Escalation of care from ward to ICU occurred in 27.3% of patients in the early corticosteroid group compared with 44.3% of patients in the standard care group (P = 0.017), new requirement for mechanical ventilation occurred in 21.7% and 36.6%, respectively (P = 0.025), and the mortality rate for the respective groups was 13.6% versus 26.3% (P = 0.024). 

Acute respiratory distress syndrome (ARDS) occurred in 26.6% of patients in the corticosteroid group and in 38.3% of patients in the standard treatment group (P = 0.04).

Patients in the corticosteroid group had a median hospital length of stay of 5 days compared with 8 days in the standard treatment group (P< 0.001).

“In this quasi-experimental study, hospitalised patients with moderate to severe COVID-19 who received an early short course of methylprednisolone had a reduced rate of the primary composite endpoint of death, ICU transfer, and mechanical ventilation, with a number needed to treat of 8 to prevent 1 patient transfer for mechanical ventilation,” the authors wrote. “The reduction in ICU transfer and requirement for mechanical ventilation represents a potential intervention to reduce critical care utilisation during the COVID-19 pandemic. The median reduction of hospital length of stay by 3 days observed with the use of corticosteroids, could positively impact hospital capacity during the COVID-19 surge.”

The authors noted that timing is crucial when it comes to administering corticosteroids in patients with COVID-19. In general, corticosteroids are not routinely recommended without an alternate indication or presence of ARDS. They said "data are conflicting; corticosteroid use in previous viral respiratory illnesses have demonstrated delayed viral clearance and increased mortality". However, there have been reports that a short course of corticosteroids is beneficial and safe in critically ill patients with COVID-19.

“The present study findings support that timing is key,” the authors wrote. “An early course of corticosteroid, specifically methylprednisolone, at the onset of dyspnoea, may attenuate progression to the hyper-inflammation phase that requires escalation of care in patients with COVID-19.”

SOURCE: Clinical Infectious Diseases