Beneficial Effects of Pulse Methylprednisolone Therapy in COVID-19 Patients at Risk of Hyperinflammatory Response.

RATIONALE: Pulse methylprednisolone therapy can prevent cytokine storm in patients with severe COVID-19. The beneficial effects of pulse methylprednisolone therapy in terms of survival and duration of hospitalization in severe COVID-19 patients have not been explicitly demonstrated. Although prior studies have reported favorable outcomes, many were limited by small sample sizes, inconsistent steroid regimens, or lack of control groups. This study explicitly evaluates the efficacy of pulse methylprednisolone through matched-group comparison with well-defined biochemical and clinical endpoints.

OBJECTIVE: This study was performed to evaluate the efficacy of pulse methylprednisolone therapy in severe COVID-19 patients at risk of hyperinflammatory response. Efficacy was measured by early mortality (Day 3), discharge rate, peripheral capillary oxygen saturation improvement, oxygen requirement reduction, and changes in inflammatory markers (C-reactive protein, CRP; interleukin-6, IL-6; D-dimer; ferritin; and LDH).

METHODS: This was a retrospective observational study. Ninety patients with confirmed COVID-19, who were at risk of a hyperinflammatory response and had elevated serum inflammatory markers, as well as critically ill COVID-19 patients, were treated with pulse methylprednisolone therapy. This therapy involved administering doses of 125, 250, and >250 mg twice daily, tailored according to severity indicators and IL-6 thresholds, in addition to standard treatment for a duration of three days (Group A). Ninety age-, gender-, and disease severity-matched COVID-19 patients were taken as controls and were treated with standard treatment alone (Group B). The primary outcomes were the mortality rate at Day 3 and the duration of hospitalization.

RESULTS: There were significant differences in the mortality rate at Day 3 (16.7% vs. 52.2%, p < 0.05) and the duration of hospitalization, 10.9 (3-22) vs. 15.3 (1-30) days, between Groups A and B. Pulse methylprednisolone therapy significantly improved the recovery (discharge) rate (83.3% vs. 47.8%), oxygen saturation (92% vs. 86%), and oxygen requirement (10 vs. 12 L/minute) compared with standard treatment alone at the end of treatment and discharge/death. There were significant improvements in inflammatory markers, including CRP, D-dimer, IL-6, ferritin, and lactate dehydrogenase levels, in Group A compared with those in Group B. No immediate adverse events with pulse methylprednisolone therapy were reported; formal monitoring protocols were limited due to retrospective design. Long term adverse effects such as secondary infections or hyperglycemia were not assessed due to study design.

CONCLUSIONS: Adjunct pulse methylprednisolone therapy significantly improved mortality rate, duration of hospitalization, enhanced recovery rate, decreased oxygen requirement, and improved laboratory parameters compared to standard treatment alone in patients with severe COVID-19 at risk of hyperinflammatory response. These benefits may be attributed to pulse methylprednisolone's rapid onset of action and potent nongenomic anti-inflammatory effects, which allow for faster suppression of key cytokines such as IL-6 and CRP. This mechanistic advantage may explain its superior efficacy over conventional corticosteroids like dexamethasone in mitigating the cytokine storm associated with severe COVID-19. Further prospective studies are warranted to confirm these findings and assess long-term safety outcomes.