Dexamethasone in hospitalized patients with COVID-19 preliminary report: Discussions from the respirology and sleep Twitter journal club @respandsleepjc (#rsjc)

Abstract

The COVID-19 pandemic has been a significant challenge for health systems worldwide. While the infection most often causes mild disease, a substantial proportion of patients develop hypoxemia, which can progress to acute respiratory distress syndrome (ARDS), associated with a high degree of morbidity and mortality. Severe COVID-19 causes diffuse alveolar damage and microvascular thrombosis, and the host immune response plays a key role in the pathophysiology of similar viral pneumonias (including avian influenza, SARS, and seasonal influenza). Given the elevation noted in inflammatory markers such as C-reactive protein, ferritin, IL-1, and IL-6, a similar pathophysiology is postulated in COVID-19.1 Several medications have been studied and showed either mixed or marginal benefit. Remdesivir showed a reduction in hospital length of stay and symptoms,2 and hydroxychloroquine3 and azithromycin4 showed a lack of efficacy. Methylprednisolone showed a reduction in a composite of mortality, intensive care admission, and noninvasive ventilation initiation in a partially randomized observational study.5 In this context, the RECOVERY trial (Randomized Evaluation of COVID-19 Therapy) was an unblinded, randomized controlled trial looking at multiple COVID-19 treatments. Prior to this study case fatality was 37% among patients requiring mechanical ventilation.6 Patients were randomized to one of usual care, dexamethasone, hydroxychloroquine, azithromycin, or lopinavir-ritonavir. When convalescent plasma became available, it was also added to the study as a separate intervention with its own control. If patients were to worsen in any arm, they would be randomized to either tocilizumab as rescue therapy or continue usual care. Initial findings from the study were revealed through press releases and preprints. The first published report from RECOVERY evaluated dexamethasone,6 and this was reviewed at our Twitter-based journal club (@respandsleepjc, #rsjc). The critical appraisal is found in Table 1, where we appraised the validity of the study, and Table 2, where we critically appraise the results of the trial. Ultimately, the study found that dexamethasone, at a dose of 6 mg orally or intravenously, once daily reduced all-cause mortality by 2.8%. This was driven by a mortality reduction in patients on oxygen (absolute risk reduction 2.9%), and among mechanically ventilated patients (ARR 12.1%). In patients on room air, mortality rates were numerically higher among patients on dexamethasone (17.8% vs. 14.0%) but the difference did not reach statistical significance.6