Second Week Methyl-Prednisolone Pulses Improve Prognosis in Patients With Severe Coronavirus Disease 2019 Pneumonia: An Observational Comparative Study Using Routine Care Data

Abstract

OBJECTIVE: To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) on the clinical course of patients with severe coronavirus disease 2019 (COVID-19) pneumonia. DESIGN: Comparative observational study using data collected from routine care. SETTING: Hospital Universitario Cruces, a tertiary level University hospital at Barakaldo, Bizkaia, Spain. PARTICIPANTS: All patients with COVID-19 pneumonia admitted between 1st March and 30th April 2020 to the services of Infectious Diseases and Internal Medicine. INTERVENTIONS: Treatment with week-2-MP (125-250 mg/d for 3 consecutive days with no subsequent tapering) vs. standard of care. MAIN OUTCOMES MEASURES: Time to death and time to death or endotracheal intubation. RESULTS: Two hundred and forty-two patients with confirmed COVID-19 pneumonia and elevated inflammatory markers at admission were included in the study. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died during the study period. Thirty-one patients (12.8%) suffered death or intubation. The adjusted HR for death was 0.35 (95%CI 0.11 to 1.06, p= 0.064) for patients in the week-2-MP group. The adjusted HR for death or intubation week-2-MP was 0.33 (95%CI 0.13 to 0.84, p=0.020) for patients in the week-2-MP group. These differences were seen in the subcohort of patients with a SaO2/FiO2 at day 7 lower than the median of the whole population: HR 0.31, 95% CI 0.08 to 1.12, p=0.073 and HR 0.34, 95%CI 0.12 to 0.94, p=0.038, respectively, but not in patients with higher SaO2/FiO2. Other predictors of the final outcomes were arterial hypertension, SaO2/FiO2, high-risk CURB65 scores and the use of non-pulse glucocorticoids. Non-pulse glucocorticoids were a predictor of infections (OR 4.72, 95%CI 1.90 to 11.80, p<0.001), while week-2-MP were not (OR 1.04, 95%CI 0.40 to 2.70, p=0.938). CONCLUSIONS: Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point. REGISTRATION: This study has been registered in the EU PAS Register with the number EUPAS36287.

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“…So far, there is no specific antiviral drug that is effective. Even in the face of many controversies, Corticosteroid is an essential [2,68] option in alleviating the symptoms caused by the cytokine storm, responsible for the period in which many orotracheal intubations occur (OTI), especially in people with predictors of severity (mainly obese, diabetic, and elderly) because they already have an inflammatory profile related to their comorbidities [40,[69][70][71].…”

SARS-CoV-2: Current trends in emerging variants, pathogenesis, immune responses, potential therapeutic, and vaccine development strategies

“… [227] , [228] , [229] corticosteroids (Methylprednisolone) Some studies showed that low doses of methylprednisolone effectively improved the prognosis of patients with severe COVID-19 pneumonia if used before the onset of ARDS. [234] , [235] Cytokine inhibitors IL-6 inhibitors (Tocilizumab) TNF-α inhibitors (Infliximab) Tocilizumab and Sarilumab are recombinant- monoclonal antibodies against the IL-6 receptor. Although several studies have shown that Tocilizumab does not prevent death in acute patients, TCZ appears to be an effective treatment option in COVID‐19 patients with a risk of cytokine storms.…”

“…Dexamethasone has more and quick antiinflammatory effects to control the cytokine storm-mediated damage of COVID-19 patient lung tissue, compared to other corticosteroids, including hydrocortisone, prednisone, or methylprednisolone [233] . Some studies however showed that Low dose and Short-course methylprednisolone effectively improved the prognosis of patients with severe COVID-19 pneumonia if used before the onset of ARDS [234] . A study showed that the use of systemic glucocorticoids did not reduce mortality and prolonged the duration of hospitalization of non-severe but advanced COVID-19 patients [235] .…”

Pathogenesis‐directed therapy of 2019 novel coronavirus disease

“…The 28-day death rate from this study 240 was six deaths in the methylprednisolone group versus 21 deaths in the control group. A third study 242 that used the second week pulsing of low-dose methylprednisolone noted that this was effective in improving the prognosis of patients with severe COVID-19 pneumonia. Several reviews 243,244 of the use of corticosteroids in COVID-19 found that in adults with COVID-19, the use of systemic glucocorticoids did not reduce mortality and prolonged the duration of hospitalization.…”

“…214 Reviews of antiviral options and the theoretical reasons for their use in the therapy of COVID-19 have been published. [241][242][243][244][245] In the following sections, only those antiviral agents that have demonstrated reasonable efficacy in COVID-19 patients will be reviewed in detail.…”