Is IV Methylprednisolone Pulse Therapy of Benefit in COVID-19 Pneumonia?

IV drip
IV drip.
Pulse glucocorticoid therapy effectively treats immuno-inflammatory conditions associated with COVID-19, but is it effective for COVID-19 pneumonia?

Adding intravenous (IV) pulse glucocorticoid therapy to standard low-dose dexamethasone has no benefit in treating COVID-19 pneumonia, according to study findings recently published in the European Respiratory Journal.

Pulse glucocorticoid therapy is used for severe or life threatening immuno-inflammatory conditions associated with COVID-19, including the cytokine storm inflammatory process. Adding IV pulse glucocorticoid therapy to the standard low-dose dexamethasone regimen can quell the hyperinflammatory processes in COVID-19 better than dexamethasone alone. However, no double-blind randomized trial has ever assessed the effectiveness of adding steroid pulse therapy to standard care for COVID-19 pneumonia.

The double-blind, randomized, placebo-controlled trial ( Identifier, NCT04673162) was conducted at 19 hospital in the Reggio Emilia region of Italy. The researchers randomized 304 hospitalized COVID-19 pneumonia patients into 2 groups; 1 group received 1 g methylprednisolone intravenously for 3 consecutive days, and the other group received placebo. Both groups received the standard dose of dexamethasone.

Of the 304 patients initially selected for the study, 149 patients (98.7%) in the methylprednisolone pulse cohort and 148 (98.7%) in the placebo cohort received the therapy as assigned. Most participants, 144/151 (95.4%) in the active treatment group and 142/150 (94.7%) in the placebo group received all 3 pulses. In all, 112 of 151 (75.4%) patients in the pulse methylprednisolone cohort and 111 of 150 (75.2%) in the placebo cohort were released from the hospital without oxygen within 30 days of randomization. Both groups had roughly the same median time to discharge (15 days; [95% CI, 13.0-17.0] and 16 days [95% CI, 13.8-18.2]); hazard ratio (HR), 0.92; 95% CI, 0.71-1.20; P =.528).

No significant differences were seen between the pulse methylprednisolone and placebo groups in admission to the intensive care unit (ICU) with orotracheal intubation or death (20.0% vs 16.1%; HR, 1.26; 95% CI, 0.74-2.16; P =.176) or overall mortality (10.0% vs 12.2%; HR, 0.83; 95% CI, 0.42-1.64; P =.584). Patients in both groups experienced serious adverse events with comparable frequency.

The primary outcome was length of hospitalization, determined as the time between randomization and hospital discharge without the need of supplementary oxygen. The main secondary outcomes were survival without invasive ventilation and overall survival. No significant difference was observed in time to hospital discharge between the high-dose methylprednisolone pulse patients and the standard care patients, and no benefit was noted in the secondary outcomes, survival and admission to the ICU. Overall, the similarities in outcomes in both arms of the trial indicated that methylprednisolone provided no additional positive effects.

Strengths of the trial included its multicenter, double-blind, placebo-controlled status. Choosing a patient population with a severe inflammatory status allowed patients in both groups to have a better chance of responding to the methylprednisolone pulses. The 2 groups also were balanced in baseline demographics, days from symptom onset to randomization, Pao2/fraction of inspired oxygen (FIO2) value, noninvasive support therapy at randomization, coexisting conditions, and concurrent treatment. The most important limitation of the trial was its modest sample size.

“The lack of benefit on the primary outcome detected in the ITT (intention-to-treat) population was also observed in subgroups of patients defined according to different Pao2/FIO2 values, different modalities of oxygen therapy, and different CRP (C-reactive protein) values at randomization,” the authors stated. “Therefore, a rapid and vigorous suppression of inflammation with the addition of methylprednisolone pulses did not provide clinical benefit compared to standard care with dexamethasone,” they declared.


Salvarani C, Massari M, Costantini M, et al. Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial. Eur Respir J. Published online March 31, 2022. doi:10.1183/13993003.00025-2022