A living WHO guideline on drugs for covid-19

Clinical question: What is the role of drugs in the treatment of patients with covid-19?New recommendation: Pre-prints of four randomised trials (from a larger adaptive randomised master protocol) among patients with non-severe illness, and the RECOVERY trial among severe and critically ill patients, triggered this guideline update. This resulted in a conditional recommendation to use a combination of casirivimab and imdevimab in non-severe patients for those at highest risk of severe disease. The RECOVERY trial included a crucial subgroup analysis demonstrating differential benefits (effect modification) associated with serological status. The Guideline Development Group (GDG) made a second conditional recommendation to use casirivmab-imdevimab in patients with severe and critical infection, if the individual has seronegative status.Prior recommendations: (a) A strong recommendation for interleukin-6 receptor blockers (tocilizumab or sarilumab) in patients with severe or critical covid-19; (b) a recommendation not to use ivermectin in patients with covid-19, regardless of disease severity, except in the context of a clinical trial; (c) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (d) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (e) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (f) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19; and (g) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created: This living guideline, from the World Health Organization (WHO), provides up to date covid-19 guidance to inform policy and practice worldwide. MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network meta-analysis informed the recommendations. A GDG of content experts, clinicians, patients, ethicists, and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation: In patients with non-severe illness, pooled data showed casirivimab-imdevimab had trivial or no effects on mortality or need for mechanical ventilation, due to very low baseline risk. Evidence demonstrated a likely reduction in need for hospitalisation; the absolute benefit will be greater in those at highest risk of hospitalisation. When moving from evidence to the conditional recommendation to use casirivimab-imdevimab in those at highest risk, the GDG recognised the limited availability, in relation to the large number of patients with non-severe disease, of the medicine and the very small benefits in reducing hospitalisation for low risk patients. Although there is no established decision tool to identify those at highest risk of hospitalisation, factors that substantially increase risk include no prior vaccination, older age, immunosuppression, and the presence of chronic conditions. In patients with severe or critical illness the conditional recommendation reflects the likelihood that any benefits are restricted to patients who are seronegative. A credible subgroup effect demonstrated that, in patients who are seronegative (that is, absence of their own anti-SARS-CoV-2 spike protein antibodies despite active infection), casirivimab-imdevimab probably reduces mortality and may reduce the need for mechanical ventilation. Rapid identification of serological status at the time of presentation of severe or critical illness is necessary. Several rapid, relatively inexpensive tests with adequate performance characteristics are available.Updates: This is a living guideline. It replaces earlier versions (4 September, 20 November, 17 December 2020, 31 March 2021, and 6 July 2021) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers\u27 note: This is the sixth version (update 5) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity