What is the role of corticosteroids (such as dexamethasone) in the treatment of coronavirus disease 2019 (COVID-19)?

Updated: Nov 16, 2020
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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The UK RECOVERY trial assessed the mortality rate at day 28 in hospitalized patients with COVID-19 who received low-dose dexamethasone 6 mg PO or IV daily for 10 days added to usual care. Patients were assigned to receive dexamethasone (n = 2104) plus usual care or usual care alone (n = 4321). Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (P< 0.001). In the dexamethasone group, the incidence of death was lower than the usual care group among patients receiving invasive mechanical ventilation (29.3% vs 41.4%) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs 26.2%), but not among those who were receiving no respiratory support at randomization (17.8% vs 14%). [291]

Corticosteroids are not generally recommended for treatment of viral pneumonia. [292] The benefit of corticosteroids in septic shock results from tempering the host immune response to bacterial toxin release. The incidence of shock in patients with COVID-19 is relatively low (5% of cases). It is more likely to produce cardiogenic shock from increased work of the heart need to distribute oxygenated blood supply and thoracic pressure from ventilation. Corticosteroids can induce harm through immunosuppressant effects during the treatment of infection and have failed to provide a benefit in other viral epidemics, such as respiratory syncytial virus (RSV) infection, influenza infection, SARS, and MERS. [293]

Early guidelines for management of critically ill adults with COVID-19 specified when to use low-dose corticosteroids and when to refrain from using corticosteroids. The recommendations depended on the precise clinical situation (eg, refractory shock, mechanically ventilated patients with ARDS); however, these particular recommendations were based on evidence listed as weak. [294] The results from the RECOVERY trial in June 2020 provided evidence for clinicians to consider when low-dose corticosteroids would be beneficial. [291]

Several trials examining use of corticosteroids for COVID-19 were halted following publication of the RECOVERY trial results. However, a prospective meta-analysis from the WHO rapid evidence appraisal for COVID-19 therapies (REACT) pooled data from 7 trials (eg, RECOVERY, REMAP-CAP, CoDEX, CAP COVID) that totaled 1703 patients (678 received corticosteroids and 1025 received usual care or placebo). An association between corticosteroids and reduced mortality was similar for dexamethasone and hydrocortisone, suggesting the benefit is a general class effect of glucocorticoids. The 28-day mortality rate, the primary outcome, was significantly lower among corticosteroid users (32% absolute mortality for corticosteroids vs 40% assumed mortality for controls). [295] An accompanying editorial addresses the unanswered questions regarding these studies. [296]   

WHO guidelines for use of dexamethasone (6 mg IV or oral) or hydrocortisone (50 mg IV every 8 hours) for 7-10 days in the most seriously ill patients coincides with publication of the meta-analysis. [297]   

A study describing clinical outcomes of patients diagnosed with COVID-19 was conducted in Wuhan, China (N = 201). Eighty-four patients (41.8%) developed ARDS, and of those, 44 (52.4%) died. Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).113 

Researchers at Henry Ford Hospital in Detroit implemented a protocol on March 20, 2020, using early, short-course, methylprednisolone 0.5-1 mg/kg/day divided in 2 IV doses for 3 days in patients with moderate-to-severe COVID-19. Outcomes of pre- and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, or mortality was the primary outcome measure. All patients had at least 14 days of follow-up. They analyzed 213 eligible patients, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in the post-corticosteroid group than in the pre-corticosteroid group (34.9% vs 54.3%; P = 0.005). This treatment effect was observed within each individual component of the composite endpoint. A significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs 5 days; P< 0.001). [298]

A study in the Netherlands showed that a 5-day course of high-dose corticosteroids accelerated respiratory recovery, lowered hospital mortality rates, and reduced the likelihood of mechanical ventilation in patients with severe COVID-19–associated cytokine storm syndrome compared with historical controls. Forty-three percent of patients also received tocilizumab. [299]

A retrospective study at Montefiore Hospital in the Bronx borough of New York was conducted to evaluate if early glucocorticoid treatment (ie, within 48 hours of admission) reduced mortality rates or the need for mechanical ventilation in hospitalized patients with COVID-19. Of the 1,806 patients included in the study, 140 (7.7%) were treated with glucocorticoids, and 1,666 patients never received glucocorticoids. A key finding of this analysis is the need to verify which patients should receive glucocorticoid treatment. Glucocorticoid use in patients with initial C-reactive protein (CRP) levels of 20 mg/dL or greater was associated with significantly reduced risk of mortality or mechanical ventilation (OR, 0.23; 95% CI, 0.08-0.70), while use in patients with a CRP level of less than 10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). [300]

An investigational suprapharmacologic dexamethasone sodium phosphate formulation (AVM0703; Seattle AVM Biotechnology) is starting in phase 1 and 2 trials to determine how it quickly it mobilizes natural killer T- (NKT), cytotoxic T-, and dendritic cells to treat ARDS.{ref 537}


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