Methylprednisolone Pulses in Hospitalized COVID-19 Patients Without Respiratory Failure: A Randomized Controlled Trial

Abstract

BackgroundCorticosteroids are the cornerstone of the treatment of patients with COVID-19 admitted to hospital. However, whether corticosteroids can prevent respiratory worsening in hospitalized COVID-19 patients without oxygen requirements is currently unknown.AimsTo assess the efficacy of methylprednisolone pulses (MPP) in hospitalized COVID-19 patients with increased levels of inflammatory markers not requiring oxygen at baseline.MethodsMulticenter, parallel, randomized, double-blind, placebo-controlled trial conducted in Spain. Patients admitted for confirmed SARS-CoV-2 pneumonia with raised inflammatory markers (C-reactive protein >60 mg/L, interleukin-6 >40 pg/ml, or ferritin >1,000 μg/L) but without respiratory failure after the first week of symptom onset were randomized to receive a 3-day course of intravenous MPP (120 mg/day) or placebo. The primary outcome was treatment failure at 14 days, a composite variable including mortality, the need for ICU admission or mechanical ventilation, and clinical worsening, this last parameter defined as a PaO2/FiO2 ratio below 300; or a 15% decrease in the PaO2 from baseline, together with an increase in inflammatory markers or radiological progression. If clinical worsening occurred, patients received tocilizumab and unmasked corticosteroids. The secondary outcomes were 28-day mortality, adverse events, need for ICU admission or high-flow oxygen, length of hospital stay, SARS-CoV-2 clearance, and changes in laboratory parameters.ResultsA total of 72 patients were randomized and 71 patients were analyzed (34 in the MPP group and 37 in the placebo group). Twenty patients presented with treatment failure (29.4 in the MPP group vs. 27.0% in the placebo group, p = 0.82), with no differences regarding the time to treatment failure between groups. There were no cases of death or mechanical ventilation requirements at 14 days post-randomization. The secondary outcomes were similar in MPP and placebo groups.ConclusionsA 3-day course of MPP after the first week of disease onset did not prevent respiratory deterioration in hospitalized COVID-19 patients with an inflammatory phenotype who did not require oxygen.

Glucocorticoid Therapy in COVID-19

“…12 Table 3 summarizes the main RCTs regarding the use of glucocorticoids in COVID-19. 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 Several RCTs have proven the efficacy and safety of corticosteroids in COVID-19. 77 78 79 80 81 82 However, several factors should be considered.…”

“…However, no data are available on patients with SpO 2 values between 90 and 93%. 83 Severity of COVID-19 was assessed based on clinical data and only three studies considered the degree of systemic inflammation (e.g., serum C-reactive protein and IL-6) as an inclusion criterion. 81 82 83 Indeed, inflammation could be regarded as a “treatable trait” in patients with SARS-CoV-2 infection.…”

“…90 Favorable results were obtained with corticosteroids given at boluses in early phases of disease in patients requiring oxygen and with elevated inflammatory biomarkers, 81 whereas there was no clear benefit in those without respiratory insufficiency. 83 So far, there is no unique opinion on which steroid dosage could optimize the cost-to-benefit ratio, and further research is required on this topic. Inflammation-based endotyping might be helpful in choosing the right doses of glucocorticoids for patients with COVID-19.…”

“…However, there was much heterogeneity in the definition of end points among different research groups. 77,[79][80][81][82][83]87,89,90 In two cohorts, glucocorticoid administration reduced the need for intensive care, respiratory, or cardiovascular support. In both cases, no difference in mortality could be observed.…”

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

“…Системные глюкокортикостероиды. По результатам нескольких рандомизированных исследований наиболее часто регистрируемой НР при использовании системных глюкокортикостероидов была гипергликемия (26,5-32,3%) [30][31][32][33], которая встречалась хотя бы один раз при применении всех изученных препаратов, Таблица 5. Нежелательные реакции при применении вируснейтрализующих антител у пациентов с COVID-19 [35] сообщалось о нескольких случаях НР при применении ингаляционного глюкокортикостероида будесонида: боль в горле (4 чел.)…”