The ten reasons why corticosteroid therapy reduces mortality in severe COVID-19
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EDITORIAL
The ten reasons why corticosteroid therapy reduces mortality in severe COVID‑19 Yaseen M. Arabi1* , George P. Chrousos2 and G. Umberto Meduri3,4 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
The recent finding of the effectiveness of corticosteroid therapy in reducing mortality in patients with severe coronavirus disease-19 (COVID-19) is a welcome breakthrough [1–6]. In this article, we highlight the current understanding of the effect of corticosteroid therapy in severe COVID-19. 1. Evidence of effectiveness from randomized controlled trials in hospitalized patients with COVID-19. The RECOVERY randomized controlled trial (RCT) demonstrated that dexamethasone (6 mg daily for 10 days) in hospitalized patients with COVID-19 reduced (i) 28-day mortality (rate ratio 0.83; 95% confidence interval [CI], 0.75–0.93), (ii) duration of hospitalization and (iii) progression to invasive mechanical ventilation [1]. The greatest mortality reduction was observed in those receiving oxygen supplementation or invasive mechanical ventilation; no improvement was observed in those without respiratory support [1]. A prospective meta-analysis of 7 RCTs further confirmed the benefit of corticosteroid therapy in reducing mortality critically ill patients with COVID-19 (summary odds ratio [OR] 0.66, 95% CI, 0.53-0.82) [2]. This is the best direct evidence supporting corticosteroid therapy in severe COVID-19. 2. Evidence of effectiveness in non-viral acute respiratory distress syndrome (ARDS). A recent Spanish RCT (n = 277) of patients with moderate-to-severe ARDS, found that dexametha-
*Correspondence: [email protected] 1 Intensive Care Department, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia Full author information is available at the end of the article
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sone (20 mg and 10 mg for 5 days each), in comparison to placebo, was associated with more mechanical ventilation-free days and lower mortality. An updated meta-analysis of ten RCTs shows that corticosteroid therapy initiated before day 14 of ARDS was associated with a significant reduction in duration of mechanical ventilation and hospital mortality (risk ratio [RR] 0.67; 95% CI 0.52–0.87) [7]. Evidence of effectiveness in community-acquired pneumonia. Several systematic reviews demonstrated that in patients hospitalized with community-acquired pneumonia (CAP), corticosteroid therapy was associated with reduction in mortality, length of stay and time to clinical stability [8]. Dysregulated immune response in COVID-19. Corticosteroid therapy aims to support the central regulatory function of the activated glucocorticoid receptor α (GC-GRα) throughout disease development and resolution. The dysregulated immune response observed in COVID-19 is qualitatively similar to that of multifactorial ARDS [9]. In patients with severe COVID-19, glucocorticoid receptor expression in bronchoalveolar lavage myeloid cells
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