WHO’s Guidelines for use of Corticosteroids in COVID-19

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WHO’s Guidelines for use of
Corticosteroids in COVID-19

Summary Clinical question: What is the role of systemic corticosteroids in the treatment of patients with COVID-19?

Target audience: The target audience consists primarily of clinicians, and, secondarily, health care decision-makers.

Current practice: Corticosteroids have received worldwide attention as a potentially effective treatment for COVID-19. This guideline was triggered on 22 June 2020 by the publication of the preliminary report of the RECOVERY trial which has now been published as a peer-reviewed paper. Corticosteroids are listed in the World Health Organization (WHO) model list of essential medicines, readily available globally at a low cost, and of considerable interest to all stakeholder groups. How this guideline was created: This guideline reflects an innovation from the WHO, driven by an urgent need for global collaboration to provide trustworthy and living COVID-19 guidance informing policy and practice worldwide during an outbreak of an emerging infectious disease, such as this pandemic. For this purpose, WHO has partnered with the non-profit Magic Evidence Ecosystem Foundation (MAGIC) for methodologic support, to develop and disseminate living guidance for COVID-19 drug treatments.

WHO also partnered with investigators of seven trials on corticosteroids to conduct a prospective meta-analysis of randomized trials for corticosteroid therapy for COVID-19 (PMA), in order to rapidly provide additional evidence to build on RECOVERY data and inform guidance development. Drawing on these data, an international panel of content experts, patients, clinicians and methodologists (no conflicts of interest declared for any of the participants) produced recommendations following standards for trustworthy guideline development using the GRADE approach. We considered an individual patient perspective and contextual factors (i.e. resources, feasibility, acceptability, equity) for countries and health care systems. The evidence: The guideline panel was informed by combining two meta-analyses which pooled data from eight randomized trials (7184 participants) of systemic corticosteroids for COVID-19. The panel discussions were also informed by two other meta-analyses, which were already published and pooled data about the safety of systemic corticosteroids in distinct but relevant patient populations.

Results: The resulting evidence summary suggested that systemic corticosteroids probably reduce 28-day mortality in patients with critical COVID-19 (moderate certainty evidence; seven studies,1703 patients; relative risk [RR] 0.80, 95% CI 0.70–0.91; absolute effect estimate 87 fewer deaths per 1000 patients, 95% CI 124 fewer to 41 fewer), and also in those with severe disease (moderate certainty evidence; one study, 3883 patients; RR 0.80, 95% CI 0.70–0.92; absolute effect estimate 67 fewer deaths per 1000 patients, 95% CI 100 fewer to 27 fewer). In contrast, systemic corticosteroids may increase the risk of death when administered to patients with non-severe COVID-19 (low certainty evidence; one study, 1535 patients; RR 1.22, 95% CI 0.93–1.61; absolute effect estimate 39 more per 1000 patients, 95% CI 12 fewer to 107 more). In addition, systemic corticosteroids probably reduce the need for invasive mechanical ventilation (moderate certainty of evidence; two studies, 5481 patients; RR 0.74, 95% CI 0.59–0.93). In contrast, harms, in the context of the mortality reduction in severe disease, are minor. Recommendations: The panel made two recommendations: a strong recommendation for systemic (i.e. intravenous or oral) corticosteroid therapy (e.g. 6 mg of dexamethasone orally or intravenously daily or 50 mg of hydrocortisone intravenously every 8 hours) for 7 to 10 days in patients with severe and critical COVID-19, and a conditional recommendation not to use corticosteroid therapy in patients with non-severe COVID-19. Understanding the recommendation: Given the moderate certainty evidence of an important reduction in the risk of death, the panel concluded that all or almost all fully informed patients with severe or critical COVID-19 would choose treatment with systemic corticosteroids. Moreover, the panel believed that other perspectives (i.e. costs, equity, feasibility of implementation), and patient values and preferences would not alter decisions. In contrast, the panel concluded that fully informed patients with non-severe COVID-19 would mostly not choose to receive this treatment given that current data indicated they would not likely derive benefit and may derive harm. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for COVID-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially life-saving therapy. Background As of 1 September2020, 25 327 098people worldwide

Ref: Clinical guidance from WHO: https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1 reference number: WHO/2019-nCoV/Corticosteroids/2020.1

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