LAUSR

The pandemic of coronavirus disease 2019 (COVID-19) has resulted in a global health crisis. Pathophysiologically, the disease has the initial phase of viral replication that could be followed by an immunologic phase, which is characterized by a systemic inflammatory response, cytokine release syndrome, acute respiratory distress syndrome (ARDS), and multisystem organ dysfunction, and associated with a considerable rate of mortality. The critical condition of the immunologic phase of the disease has raised many studies investigating the efficacy and safety of a series of anti-inflammatory agents, including proinflammatory cytokine inhibitors (anakinra, tocilizumab, sarilumab, adalimumab, infliximab), Janus kinase inhibitors (baricitinib, tofacitinib, ruxolitinib), convalescent plasma, and granulocytemacrophage colony-stimulating factors (gimsilumab, lenzilumab, namilumab), as well as nonspecific immune modulators such as corticosteroids in patients with COVID-19.1 Corticosteroids could slow the viral clearance and increase the risk of infections. Accordingly, the application of corticosteroids in patients with pulmonary infection is still a controversial issue.2 For example, in individuals with influenza-related severe pneumonia, the use of corticosteroids is associated with poor clinical outcomes, while it could decrease mortality risk in cases of Pneumocystis jirovecii pneumonia and hypoxia.3,4 Furthermore, corticosteroids have been widely investigated in patients with classic ARDS with controversial results. A systematic review and meta-analysis of 7 randomized controlled trials (RCTs) including 851 patients showed a reduced rate of mortality (risk ratio [RR], 0.75; 95% confidence interval [CI], 0.59-0.95) and duration of mechanical ventilation (mean difference, −4.93 days; 95% CI, −7.81 to −2.06 days) in the corticosteroid group compared with the placebo group.5,6 Corticosteroids are classical anti-inflammatory and immunosuppressive medicines that reduce the production of proinflammatory cytokines, such as interleukin-6, interleukin-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α, and suppress activation of both primary and secondary immune cells. The excessive activation and immune dysregulation of the innate and adaptive immune systems in the pathogenesis of COVID-19 were acknowledged at the beginning of the pandemic.1,2 Since that time, numerous studies have been conducted to evaluate the safety and efficacy of corticosteroid therapy in patients with COVID-19. The largest trial to date is the Randomized Evaluation of COVID19 Therapy (RECOVERY) trial, in which a total of 6425 hospitalized patients with COVID-19 were randomly assigned to receive dexamethasone (n = 2104) or usual care (n = 4321). The impressive results of the open-label RECOVERY trial indicated that 6 mg of dexamethasone daily for 10 days could significantly decrease mortality in hospitalized patients withCOVID-19 receiving oxygenwith (29.3% vs 41.4%; rate ratio, 0.64; 95% CI, 0.51-0.81) or without (23.3%