Glucocorticoid Dose in COVID-19

Abstract

The ongoing COVID-19 pandemic necessitates an urgent need for rapid and yet methodologically rigorous clinical trials to identify the optimal combination of safe and effective treatments as well as rapid identification of candidate treatments that are harmful or ineffective. This need is particularly acute for treatments suitable for use in resource-limited settings, which require interventions that are widely available and inexpensive.To date, few COVID-19 treatments have been shown to be effective in improving outcomes. Systemic glucocorticoids have been demonstrated to improve survival when administered to patients who are moderately or severely ill, 1,2 and are recommended in both the World Health Organization (WHO) guidance for the clinical management of COVID-19 and the National Institutes of Health COVID-19 treatment guidelines. 3,4 Although the WHO guidance does not recommend a particular glucocorticoid dose, the National Institutes of Health guidelines recommend 6 mg of dexamethasone once daily for 10 days or until hospital discharge for hospitalized adults requiring supplemental oxygen or mechanical ventilation.The prospective meta-analysis of systemic glucocorticoids from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group found that administration of systemic glucocorticoids was associated with lower 28-day all-cause mortality. 2 The included trials, which enrolled patients who were severely ill and reported a broadly consistent treatment effect, evaluated daily glucocorticoid equivalent doses that ranged from 6 mg to 20 mg of dexamethasone. The treatment effects were similar with lowdose vs high-dose regimens. 2 No determination could be made regarding dosage, and further evidence is needed to answer the question of optimal glucocorticoid dose. A more recent Cochrane review 5 found no completed studies enabling a comparison of different doses of glucocorticoids for COVID-19.In this issue of JAMA, the COVID STEROID 2 Trial Group 6 reports the results of an international, multicenter randomized clinical trial that compared 2 alternative doses of glucocorticoids in critically ill patients with COVID-19. The investigators randomly assigned 1000 patients with confirmed SARS-CoV-2 infection who were receiving supplemental oxygen at a flow rate of at least 10 L/min or mechanical ventilation to receive, as blinded study medication, either 12 mg/d of dexamethasone or 6 mg/d of dexamethasone. 6 The median duration of prior treatment with dexamethasone was 1 day. The primary outcome was the number of days alive without life support (defined as invasive mechanical ventilation, circulatory support, or kidney replacement therapy) censored

Strongyloides coinfection in COVID‐19 patients treated with corticosteroids: A systematic review

“…Estimating the prevalence of SARS‐CoV‐2–parasite co‐infections is of particular importance for designing and implementing treatment regimens. A course of corticosteroids is one of the mainstays of COVID‐19 treatment in patients with severe or critical disease 7,68,69 . The ‘HSE Interim Guidance for the use of Systemic Corticosteroids in the Management of Hospitalised Patients with Severe COVID‐19 Disease’ provides guidelines on systemic corticosteroid use in Ireland 70 .…”

“…A course of corticosteroids is one of the mainstays of COVID-19 treatment in patients with severe or critical disease. 7,68,69 The 'HSE Interim Guidance for the use of Systemic Corticosteroids in the Management of Hospitalised Patients with Severe COVID-19…”

Higher- versus Lower-Dose Corticosteroids for Severe to Critical COVID-19: A Systematic Review and Dose–Response Meta-analysis

“…Importantly, this is the intended dose, not the actual dose administered, as many die before they can complete the course and receive less than the intended dose. Although the outcomes are presented as continuous per increment increase in corticosteroid dose, we present our results comparing 12 mg/d for 10 days of dexamethasone equivalent with 6 mg/d for 10 days of dexamethasone equivalent, representing the range of doses most commonly considered in trials that have head-to-head comparisons (i.e., RECOVERY administered 6 mg/d for 10 d and COVID-STEROIDS-2 administered 12 mg/d for 10 d) ( 18 ). We present the results as such to improve clinical utility and understanding but does not restrict the analysis to these two comparisons between any two doses that can be derived by using the linear assumptions from the analysis, within the studied doses (0–160 mg).…”

Dexamethasone doses in patients with COVID‐19 and hypoxia: A systematic review and meta‐analysis

“…2,3 However, uncertainty regarding the optimal dose of dexamethasone exists. 4 In 2021, we planned to conduct a prospective meta-analysis of six randomised clinical trials (RCTs) comparing the effects of higher versus standard doses of dexamethasone in adult patients hospitalised with COVID-19 and hypoxia. 5 While awaiting the results of these six prospectively identified trials, other relevant trials were published.…”

“…Consequently, systemic corticosteroids (e.g., dexamethasone 6 mg daily for 10 days) are now standard of care in patients with severe and critical COVID‐19 2,3 . However, uncertainty regarding the optimal dose of dexamethasone exists 4 …”