Print Page   |   Sign In   |   Join!
News & Press: Student Submissions

Corticosteroids for the Treatment of COVID-19: Literature Review & Current Guideline Recommendations

Tuesday, September 29, 2020  
Share |

Julia Fadul, PharmD Candidate, Duquesne University

Lauren Finoli, PharmD, BCPS, BCCCP, Allegheny General Hospital

Evan Westlake, PharmD, Allegheny General Hospital

Background

In late 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), better known as the novel coronavirus or COVID-19, emerged out of China causing a global pandemic. COVID-19 is associated with lung injury that can progress to respiratory failure, acute respiratory distress syndrome (ARDS), and even death. Since the beginning of the pandemic, several therapies have been studied for the treatment of COVID-19. Prior to the RECOVERY trial, no large-scale randomized control trials existed to support the use of corticosteroids in treatment of hospitalized patients with COVID-19.1

Corticosteroids have been studied in previous respiratory viruses such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). In the initial months of the COVID-19 pandemic, steroids were not the focus of attention, largely due to the results of studies from both the SARS and MERS outbreak.2

A retrospective study by Cheng and colleagues studied the efficacy and safety profiles of corticosteroid therapy in severe in SARS patients. 401 patients with were studied, including both critically ill and non-critically ill patients with confirmed SARS infection. The study found no mortality benefit in patients that received corticosteroids over those that did not.2

A multi-center, retrospective, cohort study by Yaseen and colleagues was conducted in 14 Saudi Arabian Hospitals that investigated the association of corticosteroid therapy on mortality and on MERS CoV RNA clearance. 309 patients were eligible for the study; of those, 151 received corticosteroid therapy. The most commonly administered corticosteroids were hydrocortisone and methylprednisolone. The results of this study revealed that patients in the corticosteroid group received more invasive ventilation, nitric oxide, neuromuscular blockers, vasopressors, blood transfusions, and renal replacement therapy than those in the control group. Corticosteroid therapy was also associated with higher 90-day mortality.3

The disease progression timeline observed in SARS and MERS differs from COVID-19, where it is thought that viral shedding peaks in the first few days of illness.2 The serious complications associated with COVID-19 are consequences of the body’s inflammatory response to the infection, indicating that treatment with steroids may provide some benefit. This is similar to the host immune response that plays a key role in the pathophysiology of organ failure in certain respiratory illnesses such as pneumonia.1 However, the use of corticosteroids in the treatment of pneumonia has been widely debated due to lack of evidence suggesting benefit.

Literature Summary:

Impact of Glucocorticoid Treatment in SARS-COV2 Infection Mortality4

A single-center, retrospective, controlled cohort study was conducted at a university hospital in Madrid, Spain to determine the role of steroids on in-hospital mortality in patients with confirmed COVID-19 infection. 463 patients with COVID-19 and pneumonia were included in the study. Of the 463 patients, 396 were treated with steroids and 67 were assigned to the control cohort. The patients treated with steroids received 1mg/kg/day methylprednisolone or equivalent steroid dose. In-hospital mortality was 13.9% in patients treated with steroids compared to 23.9% in the control group. Steroid treatment reduced mortality by 41.8% relative to no steroid treatment.

Risk Factors Associated with ARDS and Death in Patients with COVID-19 Pneumonia in Wuhan China5

A retrospective cohort study with 201 patients with confirmed COVID-19 infection and pneumonia in Wuhan, China was conducted with 62 patients receiving methylprednisolone during their course of therapy. Of these 62 patients, 50 had ARDS. Amongst the patients that received methylprednisolone with ARDS, the mortality was 46% compared to a mortality of 61.8% in patients that did not receive methylprednisolone with ARDS(p=0.003). The administration of methylprednisolone appeared to reduce the risk of death in patients with COVID-19 that has progressed to ARDS.

Early Short Course Corticosteroids in Hospitalized Patients with COVID-196

Fadel and colleagues conducted a multi-center single pre-test, single post-test quasi experimental study with 213 patients in Michigan that included adult patients with moderate to severe COVID-19. The trial included a pre-corticosteroid protocol group and a corticosteroid protocol group. The pre-corticosteroid protocol group included patients that initially presented within the early weeks of the COVID-19 pandemic that were treated with supportive care, lopinavir-ritonavir, ribavirin, hydroxychloroquine, or remdesivir according to institutional guidelines. The corticosteroid- protocol recommended different interventions based on severity of infection and early use of corticosteroids. The protocol recommended use of methylprednisolone 0.5mg/kg/day for 2-7 days dependent on severity of illness. For those that required corticosteroids in the standard of care group, the same dose of methylprednisolone was used. The median time to steroid use in the early corticosteroid group was 2 days and 5 days in the standard of care group. The results of this experimental study indicated reductions in mortality, need for mechanical ventilation, escalation to ICU, and composite outcomes which were primary endpoints. Results also indicated a reduction in overall mechanical ventilation, progression to ARDS, and hospital length of stay.

Dexamethasone in Hospitalized Patients with COVID-19 (RECOVERY)1

The RECOVERY trial was a randomized, controlled, open-label adaptive platform trial with multiple treatment arms that investigated possible therapies for COVID-19 in 176 National Health Service organizations in the United Kingdom. The trial reported on the results of the arm investigating the use of dexamethasone in patients that were hospitalized with clinically suspected or confirmed COVID-19 infection. 2,104 patients were randomized to receive a ten-day course of 6 mg intravenous or oral dexamethasone in addition to standard care, which was compared to 4,321 patients that received standard care alone. The average duration of dexamethasone therapy observed in the trial was 6 days. Baseline data was collected to include demographics, level of respiratory support, major comorbidities, suitability for the study treatment and treatment availability based on site. Initially, patients that were pregnant or under the age of 18 were excluded from the trial, but these exclusions were later lifted to allow for their participation.

Findings from this trial report that the use of dexamethasone reduced 28-day mortality by 17% (p<0.001). The greatest benefit was seen in patients that required respiratory support. 28-day mortality was reduced in patients receiving dexamethasone requiring invasive mechanical ventilation by 35% and supplemental oxygen without invasive mechanical ventilation by 20%. There was no evidence of benefit among patients who were not receiving respiratory support.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized with COVID-19 (MetCovid)7

A parallel, double blind, placebo-controlled randomized control trial including hospitalized patients 18 years or greater with clinical, epidemiological, and/or radiological suspected COVID-19 was conducted in Manaus, Brazil. 416 patients were randomized in a 1:1 ratio to receive either methylprednisolone 0.5mg/kg/day or placebo. The primary outcome was 28-day mortality, which was not proven to be statistically different between the groups. However, patients over the age of 60 in the methylprednisolone group had lower mortality rates at day 28 compared to placebo. Patients receiving corticosteroid required more insulin therapy. 

Conclusion:

Several studies as stated above have investigated the use of corticosteroids for the treatment of COVID-19. The RECOVERY trial was the first randomized control trial conducted to analyze the effect of corticosteroids on mortality in COVID-19 patients. In fact, the RECOVERY trial proved dexamethasone to be the only medication thus far to provide any mortality benefit in these patients. The results of the trial had significant clinical implications, as dexamethasone quickly became a reasonable first-line option for COVID-19 treatment, assuming the need for respiratory support. The trial included an older population, with a range of comorbidities that accurately represents the general population affected by the virus, making this a strength of the trial. A secondary endpoint included time until discharged, which was significantly decreased in the dexamethasone group1. The results of this secondary endpoint are especially important during a global pandemic, when hospital resource demand is high.

The MetCovid trial was also a randomized control trial that investigated the use of methylprednisolone for treatment of COVID19.7 The investigation of other corticosteroids is important, especially to provide future guidance in instances of medication shortages. However, the use of methylprednisolone did not provide the same mortality benefit as dexamethasone. Perhaps this is suggestive of a benefit of the strictly glucocorticoid activity of dexamethasone.

The results of the trials reviewed above indicate that dexamethasone should be utilized in the treatment of hospitalized COVID19 patients. Dexamethasone 6 mg daily should be administered intravenously or per orally for 10 consecutive days to provide the best possible chance of observing the mortality benefit shown in the RECOVERY trial in patients with confirmed COVID-19 that require respiratory support.

Current Guideline Recommendations:

The Infectious Disease Society of America Guidelines8

IDSA recommends the use of dexamethasone 6mg IV or PO for 10 days (or equivalent glucocorticoid dose until available) for the treatment of severe COVID-19 requiring respiratory support. The IDSA recommends against the use of glucocorticoids for patients without hypoxemia requiring supplemental oxygen. This recommendation was made following the results of the RECOVERY trial.

National Institute of Health COVID-19 Treatment Guidelines9

NIH recommends the use of dexamethasone 6mg per day for up to 10 days in patients with COVID-19 that are mechanically ventilated or require supplemental oxygen. The panel recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen. This recommendation was made following the results of the RECOVERY trial.

Citations:

  1. The RECOVERY Collaborative Group, Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. N Engl J Med. (2020) July 17, doi: 10.1056/NEJMoa2021436. 

  2. Chen, et al. Treatment of Severe Acute Respiratory Syndrome with Glucosteroids. CHEST J. (2006) June 01, doi:10.1378/chest.129.6.1441

  3. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767.

  4. Fernandez-Cruz A, Ruiz-Antoran B, Munoz-Gomez A, et al. Impact of glucocorticoid treatment in SARS-CoV-2 infection mortality: a retrospective controlled cohort study. medRxiv 2020: 2020.05.22.20110544.

  5. Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.JAMA Intern Med. 2020;180(7):1-11. doi:10.1001/jamainternmed.2020.0994

  6. Fadel R, Morrison AR, Vahia A, et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa601

  7. Jeronimo, et al. Methylprednisolone as Adjunctive Therapy for Patients Hospitalized with COVID-19 (Metcovid): A randomized, double-blind, phase IIB, placebo-controlled trial. Clin Infec Disease. (2020) August 12, doi:10.1093/cid/ciaa1177

  8. Infectious Disease Society of America. Guidelines on the treatment and management of patients with COVID-19. Update: (2020) June 25. Available at: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-5

 


more Calendar

10/21/2020 » 10/22/2020
PSHP 2020 Pennsylvania Virtual Residency & Fellowship Showcase (Program Registration Only)

10/21/2020 » 10/22/2020
PSHP 2020 Pennsylvania Virtual Residency & Fellowship Showcase (Student Information)

Membership Management Software Powered by YourMembership  ::  Legal